Treatment / prevention of disease by LINC complex inhibition

Abstract

Methods for the treatment and prevention of laminopathies and diseases characterised by hyperlipidemia through LING complex inhibition are disclosed. In particular, LING complex disruption by expression of dominant-negative LING complex proteins alleviates pathophysiology in Lmna mutation-associated muscular dystrophy, progeria, and dilated cardiomyopathy. In addition, LING complex disruption by expression of dominant-negative LING complex proteins also alleviates pathophysiology in mouse models of atherosclerosis and familial hypercholesterolemia.

Description

LINC complex structure and function Linker of nucleoskeleton and cytoskeleton (LINC) complexes are polypeptide complexes comprising SUN domain-containing proteins and KASH domain-containing proteins. LINC complex structure is reviewed in e.g. in Sosa et al., Curr Opin Struct Biol. (2013) 23(2):285-91 and Hieda, Cells (2017) 6(1):3, both of which are hereby incorporated by reference in their entirety. LINC complexes connect the inner nuclear membrane (INM) and the outer nuclear membrane (ONM) or the nuclear envelope. SUN domain-containing proteins span the INM, and are associated with nuclear lamins and chromatin-binding proteins on the nucleoplasmic side of the INM, and with KASH domain-containing proteins on the perinuclear side of the INM. KASH domain-containing proteins span the ONM, and are associated with cytoskeletal structural components such as actin filaments, microtubule motors and intermediate filaments on the cytoplasmic side of the ONM, and with SUN domain-containing proteins on the perinuclear side of the ONM. SUN domain proteins function as translumenal tethers for KASH domain proteins in the ONM. Herein, a “SUN domain-containing protein” refers to any polypeptide comprising a SUN domain. SUN (Sadi and UNC-84) domain proteins are important INM components comprising conserved, carboxy terminal SUN domains which localise to the perinuclear space. SUN domains comprise ~175 residues and are provided at the end of helical stalk regions. The nucleoplasmic domains of SUN proteins interact with structural components of the nucleoskeleton. A SUN domain may comprise or consist of the amino acid sequence shown in SEQ ID NO:82, 83, 84, 85, 86 or 87, or an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence shown in SEQ ID NO:82, 83, 84, 85, 86 or 87. In some embodiments a SUN domain-containing protein is selected from SUN1, SUN2, SUN3, SUN5, SPAG4 and SUCO. In some embodiments the SUN domain-containing protein is SUN1 or SUN2. In some embodiments a SUN domain-containing protein is capable of forming a LINC complex. In some embodiments a SUN domain-containing protein is capable of interacting with a KASH domain and / or a KASH domain-containing protein. Human SUN1 is the polypeptide identified by UniProtKB 094901, the amino acid sequence of which is shown in SEQ ID NO:88. Human SUN2 is the polypeptide identified by UniProtKB Q9UH99, the amino acid sequence of which is shown in SEQ ID NO:89. Human SUN3 is the polypeptide identified by UniProtKB Q8TAQ9, the amino acid sequence of which is shown in SEQ ID NQ:90. Human SUN5 is the polypeptide identified by UniProtKB A9Z1W8, the amino acid sequence of which is shown in SEQ ID NO:91. Human SPAG4 is the polypeptide identified by UniProtKB Q9NPE6, the amino acid sequence of which is shown in SEQ ID NO:92. Human SUCO is the polypeptide identified by UniProtKB Q9UBS9, the amino acid sequence of which is shown in SEQ ID NO:93. In this specification “SUN1”, “SUN2, “SUN3”, “SUN5” “SPAG4” and “SUCO” respectively refer to SUN1, SUN2, SUN3, SUN5, SPAG4 and SUCO from any species and include isoforms, fragments, variants or homologues thereof. As used herein, a “fragment”, “variant” or “homologue” of a protein may optionally be characterised as having at least 60%, preferably one of 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence of the reference protein (e.g. a reference isoform of the reference protein). In some embodiments fragments / variants / isoforms / homologues may be characterised by ability to perform a function performed by the reference protein. A “fragment” generally refers to a fraction of the reference protein. A “variant” generally refers to a protein having an amino acid sequence comprising one or more amino acid substitutions, insertions, deletions or other modifications relative to the amino acid sequence of the reference protein, but retaining a considerable degree of sequence identity (e.g. at least 60%) to the amino acid sequence of the reference protein. An “isoform” generally refers to a variant of the reference protein expressed by the same species as the species of the reference protein. A “homologue” generally refers to a variant of the reference protein produced by a different species as compared to the species of the reference protein. Homologues include orthologues. A “fragment” may be of any length (by number of amino acids), although may optionally be at least 20% of the length of the reference protein (that is, the protein from which the fragment is derived) and may have a maximum length of one of 50%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% of the length of the reference protein. 8 Isoforms, fragments, variants or homologues may optionally be functional isoforms, fragments, variants or homologues, e.g. having a functional property / activity of the reference protein, as determined by analysis by a suitable assay for the functional property / activity. In this specification, reference to “SUN1” refers to the protein having the amino acid sequence shown in SEQ ID NO:88, and fragments, variants or homologues thereof. In some embodiments SUN1 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:88. In this specification, reference to “SUN2” refers to the protein having the amino acid sequence shown in SEQ ID NO:89, and fragments, variants or homologues thereof. In some embodiments SUN2 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:89. In this specification, reference to “SUN3” refers to the protein having the amino acid sequence shown in SEQ ID NQ:90, and fragments, variants or homologues thereof. In some embodiments SUN3 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NQ:90. In this specification, reference to “SUN5” refers to the protein having the amino acid sequence shown in SEQ ID NO:91, and fragments, variants or homologues thereof. In some embodiments SUN5 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:91. In this specification, reference to “SPAG4” refers to the protein having the amino acid sequence shown in SEQ ID NO:92, and fragments, variants or homologues thereof. In some embodiments SPAG4 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:92. In this specification, reference to “SUCO” refers to the protein having the amino acid sequence shown in SEQ ID NO:93, and fragments, variants or homologues thereof. In some embodiments SUCO comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:93. 9 Herein, a “KASH domain-containing protein” refers to any polypeptide comprising a KASH domain. KASH (Klarsicht, ANC-1, Syne homology) domain proteins are carboxy terminal-anchored membrane proteins which are targeted to the nuclear envelope. The 50-60 amino acid KASH domain is found at the C-terminus. KASH domains are hydrophobic, and comprise a single-membrane spanning helix which spans the ONM, and a ~30 amino acid region which extends into the perinuclear space. A KASH domain may comprise or consist of the amino acid sequence shown in SEQ ID NO:97, 98, 99 or 100, or an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence shown in SEQ ID NO:97, 98, 99, 100 or 101. In some embodiments a KASH domain-containing protein is selected from Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4 (also known as SYNE1, SYNE2, SYNE3 and SYNE4, respectively), KASH5 and LRMP. In some embodiments a KASH domain-containing protein is Nesprin-1, Nesprin-2 orNesprin-3. In some embodiments a KASH domain-containing protein is capable of forming a LINC complex. In some embodiments a KASH domain-containing protein is capable of interacting with a SUN domain and / or a SUN domain-containing protein. Human Nesprin-1 is the polypeptide identified by UniProtKB Q8NF91, the amino acid sequence of which is shown in SEQ ID NQ:102. Human Nesprin-2 is the polypeptide identified by UniProtKB Q8WXH0, the amino acid sequence of which is shown in SEQ ID NQ:103. Human Nesprin-3 is the polypeptide identified by UniProtKB Q6ZMZ3, the amino acid sequence of which is shown in SEQ ID NQ:104. Human Nesprin-4 is the polypeptide identified by UniProtKB Q8N205, the amino acid sequence of which is shown in SEQ ID NQ:105. Human KASH5 is the polypeptide identified by UniProtKB Q8N6L0, the amino acid sequence of which is shown in SEQ ID NQ:106. Human LRMP is the polypeptide identified by UniProtKB Q12912, the amino acid sequence of which is shown in SEQ ID NO:113. In this specification “Nesprin-1”, “Nesprin-2”, “Nesprin-3”, “Nesprin-4”, “KASH5” and “LRMP” respectively refer to Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, KASH5 and LRMP from any species and include isoforms, fragments, variants or homologues thereof. In this specification, reference to “Nesprin-1” refers to the protein having the amino acid sequence shown in SEQ ID NQ:102, and fragments, variants or homologues thereof. In some embodiments Nesprin-1 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NQ:102. 10 In this specification, reference to “Nesprin-2” refers to the protein having the amino acid sequence shown in SEQ ID NO:103, and fragments, variants or homologues thereof. In some embodiments Nesprin-2 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:103. In this specification, reference to “Nesprin-3” refers to the protein having the amino acid sequence shown in SEQ ID NQ:104, and fragments, variants or homologues thereof. In some embodiments Nesprin-3 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NQ:104. In this specification, reference to “Nesprin-4” refers to the protein having the amino acid sequence shown in SEQ ID NQ:105, and fragments, variants or homologues thereof. In some embodiments Nesprin-4 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NQ:105. In this specification, reference to “KASH5” refers to the protein having the amino acid sequence shown in SEQ ID NQ:106, and fragments, variants or homologues thereof. In some embodiments KASH5 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NQ:106. In this specification, reference to “LRMP” refers to the protein having the amino acid sequence shown in SEQ ID NO:113, and fragments, variants or homologues thereof. In some embodiments LMRP comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:113. As used herein, a “LINC complex” refers to a polypeptide complex comprising a SUN domaincontaining protein and a KASH domain-containing protein. LINC complexes are formed by protein-protein interactions between SUN domain-containing proteins and KASH domain-containing proteins. The LINC complex may comprise non-covalent and / or covalent interactions between SUN domains and KASH domains. Non-covalent interactions include e.g. hydrogen bonds, ionic interaction, Van der Waals forces and hydrophobic bonds. Covalent interactions include e.g. disulphide bonds. SUN domain proteins are thought to oligomerise to form trimers via interaction between their stalk regions to form coiled-coil triple helix (Zhou et al., J. Biol. Chern. (2012) 287: 5317-5326). Deletion of SUN domain protein stalk regions has been shown to disrupt LINC complex formation. SUN domains assume a p sandwich structure and SUN domains of the trimer interact extensively with one another in part through protruding p sheets known as KASH lids; the KASH lid of one SUN domain partially overlaps the p sandwich of the adjacent SUN domain (Sosa et al., Cell (2012) 149:1035-1047). KASH domain proteins can also oligomerise, which may involve protein-protein interactions between the transmembrane helices. A single KASH domain interacts with two adjacent SUN domains along the groove formed between the KASH lid of one SUN domain and the upper region of the p sandwich of the adjacent SUN domain. In this way, SUN and KASH domains are thought to interact to form a 3:3 hexameric heterocomplex. The 2-3 proline residues immediately prior to the C-terminus of the KASH domain are thought to be accommodated in a deep pocket within the surface of a SUN domain. This region of KASH is important for SUN-KASH interactions; extension of the C-terminus by only a single amino acid disrupts LINC complex formation. Conserved cysteine residues of SUN and KASH domains form disulphide bonds, further stabilising the SUN-KASH complex. The disulphide bonds may be important for force transmission through the LINC complex (Jahed et al., Biophys. J. (2015) 109:501-509). As explained hereinabove, LINC complexes are thought to form through the interaction of the SUN domains of three SUN domain-containing proteins and the KASH domains of three KASH domaincontaining proteins. Interaction between the SUN and KASH domain proteins is thought to be promiscuous; SUN1 and SUN2 have been shown to interact with Nesprin-1, Nesprin-2 and Nesprin-3. A LINC complex according to the present invention may comprise any SUN domain-containing protein and any KASH domain-containing protein. The SUN domain-containing proteins of the LINC complex may be identical or non-identical. The KASH domain-containing proteins of the LINC complex may be identical or non-identical. LINC complex function is reviewed in e.g. in Hieda, Cells (2017) 6(1):3 (incorporated by reference hereinabove), and Stroud, Biophys Rev. (2018) 10(4):1033-1051, hereby incorporated by reference its entirety. The LINC complex performs diverse functions, including providing structural support to the nucleus, shaping and positioning the nucleus, maintaining connection between the centrosome and the nucleus and spacing of the nuclear membrane, DNA repair, cell migration and moving chromosome within the nucleus during meiosis. The LINC complex has a mechanosensory role to translate mechanical stimuli and changes in the extracellular matrix into signals allowing the cell to adapt to its environment by modulation of cytoskeleton organization, gene expression, nuclear organisation, and structure. Integrins mediate the transduction of forces from the external microenvironment to the intracellular cytoskeleton, and nucleo-cytoskeletal molecular connections transmit the forces to chromosomal organisations in the nucleus. The nuclear lamina triggers the deformation of nuclear structures, and initiates changes in gene regulation. The nuclear envelope is a key structure in such processes. On the nucleoplasmic side of the INM, the nuclear lamina (composed of A-type and B-type lamins) forms a lattice structure which contributes to the mechanical stress resistance of the nucleus, and which is essential to the structural integrity of the nuclear envelope. Nuclear lamins are involved in processes critical to cell function and viability, including maintenance of nuclear integrity, regulation of cell cycle, mechanotransduction, cell signalling and DNA repair. Deviations from normal expression and / or function of nuclear envelope proteins, and deviations from normal expression and / or function of factors directly or indirectly associated with the nuclear envelope, are implicated in a variety of diseases including muscular dystrophies, cardiomyopathies, lipodystrophy, progeria, cancer, and neurological diseases. LINC complex inhibition The present invention is concerned with LINC complex inhibition. As used herein “LINC complex inhibition” encompass inhibition of formation of a LINC complex (i.e. inhibition of LINC complex assembly), disruption / degradation of a LINC complex, and inhibition of LINC complex activity / funotion. In some embodiments, formation of a LINC complex may be inhibited by inhibiting the gene and / or protein expression of a constituent protein of a LINC complex. Constituent proteins of LINC complexes include SUN domain-containing proteins and KASH domain-containing proteins. For conciseness, in the present specification “a constituent protein of a LINC complex” may be referred to simply as “a LINC complex protein”. In some embodiments, inhibiting formation of a LINC complex comprises one or more of: inhibiting the gene or protein expression of encoding a LINC complex protein; modifying a gene encoding a LINC complex protein to reduce / prevent its expression; reducing the level of RNA encoding a LINC complex protein; inhibiting transcription of nucleic acid encoding a LINC complex protein; increasing degradation of RNA encoding a LINC complex protein; reducing the level of a LINC complex protein; disrupt normal post-transcriptional processing (e.g. splicing, translation, post-translational processing) of RNA encoding a LINC complex protein; and increasing degradation of a LINC complex protein. Gene expression can be determined by means well known to the skilled person. The level of RNA encoding constituent proteins of LINC complexes can be determined e.g. by techniques such as RT-qPCR, northern blot, etc. A reduction in the level of RNA encoding a constituent proteins of a LINC complex may e.g. be the result of reduced transcription of nucleic acid encoding the LINC complex protein, or increased degradation of RNA encoding the LINC complex protein. Reduced transcription of nucleic acid encoding a LINC complex protein may be a consequence of inhibition of assembly and / or activity of factors required fortranscription of the DNA encoding the LINC complex protein. Increased degradation of RNA encoding a LINC complex protein may be a consequence of increased enzymatic degradation of RNA encoding the LINC complex protein, e.g. as a consequence of RNA interference (RNAi), and / or reduced stability of RNA encoding the LINC complex protein. Protein expression can be determined by means well known to the skilled person. The levels of constituent proteins of LINC complexes can be determined e.g. by antibody-based methods including western blot, immunohisto / cytochemistry, flow cytometry, ELISA, or by reporter-based methods. Protein degradation can be evaluated e.g. by detection of, or analysis of the level / proportion of, ubiquitinated protein, association with ubiquitin ligase and / or proteosomal localisation. A reduction in the level of a LINC complex protein may e.g. be the result of a reduced level of RNA encoding the LINC complex protein, reduced post-transcriptional processing of RNA encoding the LINC complex protein, or increased degradation of the LINC complex protein. Disruption to normal post-transcriptional processing of a LINC complex protein may e.g. be reduced / altered splicing of pre-mRNA to mature mRNA encoding the LINC complex protein, reduced translation of mRNA encoding the LINC complex protein, or reduced / altered post-translational processing of the LINC complex protein. Reduced / altered splicing of pre-mRNA to mature mRNA encoding the LINC complex protein may be a consequence of inhibition of assembly and / or activity of factors required for normal splicing. Reduced translation of mRNA encoding the LINC complex protein may be a consequence of inhibition of assembly and / or activity of factors required fortranslation. Reduced / altered post-translational processing (e.g. enzymatic processing, folding) may be a consequence of inhibition of assembly and / or activity of factors required for normal post-translational processing of the LINC complex protein. Increased degradation of the LINC complex protein may be a consequence of increased enzymatic (e.g. protease-mediated) degradation of the protein, which may e.g. be associated with misfolding. In some embodiments, formation of a LINC complex may be inhibited by inhibiting trafficking of, and / or disrupting normal subcellular localisation of, constituent proteins of a LINC complex (e.g. SUN domain-containing proteins and / or KASH domain-containing proteins). In some embodiments, inhibiting formation of a LINC complex comprises one or more of: reducing the level / proportion of a LINC complex protein localised to the nuclear envelope; reducing the level / proportion of SUN domaincontaining protein associated with inner nuclear membrane; reducing the level / proportion of KASH domain-containing protein associated with outer nuclear membrane; increasing retention of a LINC complex protein in the endoplasmic reticulum; and increasing the level / proportion of a LINC complex protein localised to the endoplasmic reticulum. The subcellular localisation of constituent proteins of LINC complexes within cells can be analysed using techniques known to the person skilled in the art. Such techniques include e.g. analysis by immunocytochemistry and reporter-based methods. For example, Boni et al., J. Cell Biology (2015) 209(5):705-720 and Smoyeret al., J. Cell Biology (2016) 215(4):575-590 describe a reporter system permitting imaging of proteins in the ER, INM and ONM. Such methods can be employed to analyse the levels / proportions of constituent proteins of LINC complexes in the nuclear envelope, inner nuclear membrane and an outer nuclear membrane. In some embodiments, formation of a LINC complex may be inhibited by inhibiting interaction between constituent proteins of LINC complexes (e.g. SUN domain-containing proteins and KASH domain-containing proteins). In some embodiments, formation of a LINC complex may be inhibited by inhibiting interaction between constituent proteins of a LINC complex and interaction partners for constituent proteins of a LINC complex. In some embodiments, inhibiting formation of a LINC complex comprises one or more of: inhibiting interaction between a SUN domain-containing protein and an interaction partner for a SUN domaincontaining protein; inhibiting interaction between a KASH domain-containing protein and an interaction partner for a KASH domain-containing protein; inhibiting interaction between a SUN domain-containing protein and a KASH domain-containing protein; inhibiting interaction between a SUN domain-containing protein and a lamin; inhibiting interaction between a SUN domain-containing protein and a chromatin-binding protein; inhibiting interaction between a KASH domain-containing protein and a SUN domain-containing protein; and inhibiting interaction between a KASH domaincontaining protein and a cytoskeletal component (e.g. a microfilament ora constituent thereof (e.g. actin), a microtubule or a constituent thereof (e.g. tubulin) or an intermediate filament or a constituent thereof). In some embodiments, LINC complex inhibition comprises disruption / degradation of a LINC complex. In some embodiments, LINC complex disruption / degradation comprises one or more of: inhibiting interaction between a SUN domain-containing protein and an interaction partner for a SUN domain- 15 containing protein; inhibiting interaction between a KASH domain-containing protein and an interaction partner for a KASH domain-containing protein; inhibiting interaction between a SUN domain-containing protein and a KASH domain-containing protein; inhibiting interaction between a SUN domain-containing protein and a lamin; inhibiting interaction between a SUN domain-containing protein and a chromatin-binding protein; inhibiting interaction between a KASH domain-containing protein and a SUN domain-containing protein; and inhibiting interaction between a KASH domaincontaining protein and a cytoskeletal component (e.g. a microfilament ora constituent thereof (e.g. actin), a microtubule or a constituent thereof (e.g. tubulin) or an intermediate filament or a constituent thereof); increasing LINC complex disassembly; increasing LINC complex degradation; displacing a LINC complex protein from a LINC complex; and reducing the level of a LINC complex. Herein, an interaction partner for a SUN domain-containing protein may be any molecule (e.g. protein / nucleic acid) with which SUN domain-containing protein interacts. An interaction partner for a SUN domain-containing protein may be a protein capable of forming a complex with a SUN domaincontaining protein through protein-protein interaction. In some embodiments an interaction partner for a SUN domain-containing protein may be a KASH domain-containing protein (e.g. Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4 or KASH5), a SUN domain-containing protein (e.g. SUN1, SUN2, SUN3, SUN5, SPAG4 or SUCO), a nucleoplasmic protein, a lamin (e.g. lamin A, lamin C, lamin B1 or lamin B2) ora chromatin-binding protein. Herein, an interaction partner for a KASH domain-containing protein may be any molecule (e.g. protein / nucleic acid) with which KASH domain-containing protein interacts. An interaction partner for a KASH domain-containing protein may be a protein capable of forming a complex with a KASH domain-containing protein through protein-protein interaction. In some embodiments an interaction partner for a KASH domain-containing protein may be a SUN domain-containing protein (e.g. SUN1, SUN2, SUN3, SUN5, SPAG4 or SUCO), a KASH domain-containing protein (e.g. Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, KASH5 or LRMP), a cytoplasmic protein, a cytoskeletal protein, a microfilament, actin, a microtubule, tubulin, a microtubule motor, or an intermediate filament protein. Interaction between constituent proteins of LINC complexes and interaction partners for such proteins can be analysed using techniques well known to the skilled person such as co-immunoprecipitation, and resonance energy transfer (RET) assays using appropriately labelled species. Inhibition of interaction can be determined in such assays by detection of a reduction in the level of interaction as compared to a control, uninhibited condition. LINC complexes and constituent proteins thereof may be detected e.g. using methods well known to the skilled person such as antibody-based methods including western blot, immunohisto / cytochemistry, flow cytometry, ELISA, or by reporter-based methods. LINC complex inhibition may be characterised by a reduced level of a function of a LINC complex. In some embodiments, LINC complex inhibition may be determined by detection of a reduced level of a correlate of LINC complex function. In particular embodiments contemplated herein, LINC complex inhibition is achieved by one or more of: modifying a gene encoding a SUN domain-containing protein to reduce / prevent its expression; modifying a gene encoding a KASH domain-containing protein to reduce / prevent its expression; inhibition of expression of a SUN domain-containing protein by RNAi; inhibition of expression of a KASH domain-containing protein by RNAi; or inhibiting interaction between a SUN domain-containing protein and a KASH domain-containing protein. In some embodiments modifying a gene encoding a KASH domain-containing protein or a SUN domain-containing protein to reduce / prevent its expression is achieved using a site-specific nuclease (SSN) system (e.g. a CRISPR-based system) targeting the relevant gene. In some embodiments inhibition of expression of a KASH domain-containing protein ora SUN domain-containing protein by RNAi is achieved using siRNA, miRNA or shRNA targeting the relevant protein. In some embodiments inhibiting interaction between a SUN domain-containing protein and a KASH domain-containing protein is achieved using a dominant-negative SUN domain-containing protein, a dominant-negative KASH domain-containing protein, a small molecule inhibitor of interaction between a SUN domain-containing protein and a KASH domain-containing protein, a peptidomimetic of a KASH domain or a peptidomimetic of a SUN domain. It will be appreciated that inhibition of interaction is between an endogenous SUN domain-containing protein and an endogenous KASH domaincontaining protein. LINC complex inhibitors Aspects of the present invention comprise LINC complex inhibition using a LINC complex inhibitor. A “LINC complex inhibitor” refers to any agent capable of achieving LINC complex inhibition. LINC complex inhibitors include agents capable of inhibiting formation of a LINC complex (i.e. inhibiting LINC complex assembly), disrupting / degrading a LINC complex, or inhibiting LINC complex function. Such agents may be effectors of (i.e. may directly or indirectly cause) LINC complex inhibition as described hereinabove. LINC complex inhibitors may also be referred to herein as LINC complex antagonists. In some embodiments, a LINC complex inhibitor may: inhibit formation of a LINC complex; disrupt / degrade a LINC complex; inhibit LINC complex activity; inhibit the gene and / or protein expression of a LINC complex protein; modify a gene encoding a LINC complex protein to reduce / prevent its expression; reduce the level of RNA encoding a LINC complex protein; inhibit 17 transcription of nucleic acid encoding a LINC complex protein; increase degradation of RNA encoding a LINC complex protein; reduce the level of a LINC complex protein; disrupt normal post-transcriptional processing (e.g. splicing, translation, post-translational processing) of RNA encoding a LINC complex protein; increase degradation of a LINC complex protein; inhibit trafficking of, and / or disrupt normal subcellular localisation of, a LINC complex protein; reduce the level / proportion of a LINC complex protein localised to the nuclear envelope; reduce the level / proportion of SUN domaincontaining protein associated with inner nuclear membrane; reduce the level / proportion of KASH domain-containing protein associated with outer nuclear membrane; increase retention of a LINC complex protein in the endoplasmic reticulum; increase the level / proportion of a LINC complex protein localised to the endoplasmic reticulum; inhibit interaction between constituent proteins of a LINC complex; inhibit interaction between a LINC complex protein and an interaction partner for a LINC complex protein; inhibit interaction between a SUN domain-containing protein and an interaction partner for a SUN domain-containing protein; inhibit interaction between a KASH domain-containing protein and an interaction partner for a KASH domain-containing protein; inhibit interaction between a SUN domain-containing protein and a KASH domain-containing protein; inhibit interaction between a SUN domain-containing protein and a lamin; inhibit interaction between a SUN domain-containing protein and a chromatin-binding protein; inhibit interaction between a KASH domain-containing protein and a SUN domain-containing protein; inhibit interaction between a KASH domain-containing protein and a cytoskeletal component (e.g. a microfilament or a constituent thereof (e.g. actin), a microtubule or a constituent thereof (e.g. tubulin) or an intermediate filament or a constituent thereof); increase disassembly of a LINC complex; increase degradation of a LINC complex; displace a LINC complex protein from a LINC complex; and / or reduce the level of a LINC complex. It will be appreciated that a given LINC complex inhibitor may display more than one of the properties recited in the preceding paragraph. A given agent may be evaluated for the properties recited in the preceding paragraph using suitable assays. The assays may be e.g. in vitro assays, optionally cellbased assays or cell-free assays. Where assays are cell-based assays, they may comprise treating cells with the test agent in order to determine whether the agent displays one or more of the recited properties. Assays may employ endogenously- or recombinantly-expressed proteins, and may use species labelled with detectable entities in order to facilitate their detection. Agents capable of reducing gene expression of a LINC complex protein (e.g. reducing the level of RNA encoding a LINC complex protein, reducing transcription of nucleic acid encoding a LINC complex protein and / or increasing degradation of RNA encoding a LINC complex protein) may be identified using assays comprising detecting the level of RNA encoding the relevant protein, e.g. by RT-qPCR. Such assays may comprise treating cells / tissue with the agent, and subsequently comparing the level of RNA encoding the relevant protein in such cells / tissue to the level of RNA encoding the relevant protein in cells / tissue of an appropriate control condition (e.g. untreated / vehicle- treated cells / tissue). Assays for detecting reduced / altered splicing of pre-mRNA of a given protein may comprise detecting and / or quantifying one or more isoforms of the relevant protein, or RNA encoding one or more of said isoforms. Agents capable of reducing protein expression of a LINC complex protein (e.g. reducing the level of a LINC complex protein, increasing degradation of a LINC complex protein) may be identified using assays comprising detecting the level of the relevant protein, e.g. using antibody / reporter-based methods (western blot, ELISA, immunohisto / cytochemistry, etc.). Such assays may comprise treating cells / tissue with the agent, and subsequently comparing the level of the relevant protein in such cells / tissue to the level of the relevant protein in cells / tissue of an appropriate control condition (e.g. untreated / vehicle-treated cells / tissue). Assays of protein degradation may comprise evaluating e.g. ubiquitination or proteosomal localisation of the relevant protein, and / or the proportion of the relevant protein that is ubiquitinated or localised to the proteasome. Agents capable of inhibiting trafficking and / or disrupting normal subcellular localisation of a LINC complex protein may be identified using assays comprising detecting the presence of, or determining the proportion of, the relevant protein in a given subcellular location, e.g. using antibody / reporter-based methods (western blot, ELISA, immunohisto / cytochemistry, etc.). Subcellular localisation may be analysed e.g. by immunocytochemistry, or western blot of extracts prepared from different cellular fractions, and may employ organelle markers and / or labelled proteins of known subcellular localisation. Assays may comprise treating cells / tissue with the agent, subsequently comparing the subcellular localisation of the relevant protein in such cells to the subcellular localisation of the relevant protein in cells / tissue of an appropriate control condition (e.g. untreated / vehicle-treated cells / tissue). Agents capable of inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein may be identified using assays comprising detecting the level of interaction between a LINC complex protein and an interaction partner for a LINC complex protein, e.g. using antibody / reporter-based methods. The level of interaction between a LINC complex protein and an interaction partner for a LINC complex protein can be analysed e.g. using resonance energy transfer techniques (e.g. FRET, BRET), co-immunoprecipitation or methods analysing a correlate of interaction (e.g. a function of a LINC complex). Assays may comprise treating cells / tissue with the agent, and subsequently comparing the level of interaction in such cells / tissue to the level of interaction in cells / tissue of an appropriate control condition (e.g. untreated / vehicle-treated cells / tissue). Interaction between a LINC complex protein and an interaction partner for a LINC complex protein can also be analysed e.g. using techniques such as ELISA, surface plasmon resonance or biolayer interferometry analysis. Assays may comprise comparing the level of interaction in the presence of the agent to the level of interaction in an appropriate control condition (e.g. the absence of the agent). Agents capable of inhibiting a function of a LINC complex may be identified using assays comprising detecting the level of a correlate of LINC complex function. A LINC complex inhibitor according to the present disclosure may be any agent / plurality of agents achieving the desired inhibitory activity. In some embodiments, a LINC complex inhibitor may be or comprise a peptide / polypeptide, small molecule, nucleic acid or biomolecule. In some embodiments, a LINC complex inhibitor is capable of binding to a LINC complex, a LINC complex protein, or an interaction partner for a LINC complex protein. LINC complex inhibitors may display specific binding to the relevant factor / complex (i.e. a LINC complex protein, or an interaction partner for a LINC complex protein). As used herein, “specific binding” refers to binding which is selective, and which can be discriminated from non-specific binding to non-target molecules. LINC complex inhibitors that specifically bind to a LINC complex protein or an interaction partner for a LINC complex protein preferably binds to the relevant factor with greater affinity, and / or with greater duration than other, non-target molecules; such LINC complex inhibitors may be described as being “specific for” the relevant factor. In some embodiments, a LINC complex inhibitor is capable of inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein. In some embodiments, a LINC complex inhibitor is capable of inhibiting LINC complex function. In some embodiments a LINC complex inhibitor behaves as a competitive inhibitor of interaction between a LINC complex protein and an interaction partner for a LINC complex protein. The LINC complex inhibitor may occupy, or otherwise reduce access to, a region of a LINC complex protein required for binding to an interaction partner for a LINC complex protein, or may occupy, or otherwise reduce access to, a region of an interaction partner for a LINC complex protein required for binding to a LINC complex protein. In some embodiments a LINC complex inhibitor mimics an interaction partner for a LINC complex protein. In some embodiments, a LINC complex inhibitor inhibits interaction between a SUN domain and a KASH domain. In some embodiments, a LINC complex inhibitor inhibits association between the C-terminal region of a KASH domain and the deep pocket on the surface of a SUN domain. In some embodiments a LINC complex inhibitor binds to a SUN domain and inhibits access of a KASH domain to the deep pocket of the SUN domain. In some embodiments a LINC complex inhibitor binds to a KASH domain and inhibits access of the KASH domain to a deep pocket on the surface of a SUN domain. In some embodiments, a LINC complex inhibitor inhibits the formation of, or disrupts, disulphide bonds between a SUN domain and a KASH domain. In some embodiments, a LINC complex inhibitor targets the C-terminal, proline-rich region of a KASH domain-containing protein. In some embodiments, a LINC complex inhibitor inhibits oligomerisation of SUN domain-containing proteins. In some embodiments, a LINC complex inhibitor targets the stalk region of a SUN domaincontaining protein. In some embodiments, a LINC complex inhibitor inhibits protein-protein interaction between a SUN domain and a KASH domain. In some embodiments, a LINC complex inhibitor inhibits protein-protein interaction between: SUN1 and Nesprin-1, SUN2 and Nesprin-1, SUN1 and Nesprin-2, SUN1 and Nesprin-3, SUN2 and Nesprin-2 orSUN2 and Nesprin-3. In some embodiments a LINC complex inhibitor inhibits protein-protein interaction between SUN1 and Nesprin-1. The ability of a candidate LINC complex inhibitor to inhibit interaction between a LINC complex protein and an interaction partner for a LINC complex protein can be evaluated e.g. by analysis of interaction in the presence of, or following incubation of one or both of the interaction partners with, the candidate LINC complex inhibitor. An example of a suitable assay to determine whether a given binding agent is capable of inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein is a competition ELISA. In some embodiments a molecule which binds to a LINC complex protein or an interaction partner for a LINC complex protein inhibits the ability of a LINC complex protein to bind to an interaction partner for a LINC complex protein. In some embodiments, a LINC complex inhibitor is capable of binding to a LINC complex protein or an interaction partner for a LINC complex protein, and inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein. LINC complex inhibitors which are capable of binding to a LINC complex protein or an interaction partner for a LINC complex protein, and inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein can be identified using any suitable assay for detecting binding of a molecule to the relevant factor (i.e. the LINC complex protein, or the interaction partner for the LINC complex protein) and inhibition of interaction between a LINC complex protein and an interaction partner for a LINC complex protein. Such assays may comprise e.g. detecting the formation of a complex between the relevant factor and the candidate inhibitor molecule, and / or detecting the formation of a complex between the LINC complex protein and the interaction partner for the LINC complex protein. In some embodiments, LINC complex inhibitors which are capable of binding to a LINC complex protein or an interaction partner for a LINC complex protein, and inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein may e.g. be peptide / polypeptides. A LINC complex inhibitor may e.g. be based on an interaction partner for the relevant factor (i.e. the LINC complex protein, or the interaction partner for a LINC complex protein) to which the inhibitor binds. As used herein, a peptide / polypeptide which is “based on” a reference protein comprises or consists of an amino acid sequence having high sequence identity (e.g. at least 80%, 85% 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity) to all or part of the amino acid of the reference protein. For example, a LINC complex inhibitor which binds to a LINC complex protein may comprise / consist of a peptide / polypeptide fragment of an interaction partner for a LINC complex protein. Similarly, a LINC complex inhibitor which binds to an interaction partner for a LINC complex protein may comprise / consist of a peptide / polypeptide fragment of a LINC complex protein. Such inhibitors preferably possess the ability to bind to the relevant factor, but lacks or displays a reduced level of one or more other properties of the protein on which they are based. For example, a LINC complex inhibitor may comprise the amino acid sequence(s) required for binding to the relevant factor, and may lack the amino acid sequence(s) required for one or more other properties of the protein on which it is based. Such peptide / polypeptide LINC complex inhibitors may be referred to as ‘decoy’, ‘dominant-negative’ or ‘mimetic’ versions of the proteins on which they are based, and preferably display competitive inhibition of interaction between a LINC complex protein and an interaction partner for a LINC complex protein. In this way, such peptide / polypeptide LINC complex inhibitors inhibit the formation of LINC complexes and / or disrupt existing LINC complexes via displacement of endogenous interaction partners, forming non-functional complexes / complexes having a reduced level of function. A dominant-negative version of SUN1 is described e.g. in Crisp et al. J Cell Biol. (2006) 172(1): 4153. A dominant-negative SUN2 is described e.g. in Stewart-Hutchinson et al. Exp Cell Res. (2008) 314(8):1892-905. Dominant-negative versions of KASH1 are described e.g. in Stewart-Hutch in son et al. Exp Cell Res. (2008) 314(8):1892-905, Grady et al., Proc. Natl. Acad. Sci. U.S.A. (2005) 102: 4359-4364 and Libotte et al., MBoC (2005) 16: 3411-3424. Dominant-negative versions of KASH2 are described e.g. 22 in Stewart-Hutchinson et al. Exp Cell Res. (2008) 314(8):1892-905, Libotte et al., MBoC (2005) 16: 3411-3424, Zhen et al., J. Cell. Sci. (2002) 115: 3207-3222 and Kim et al. Sci Transl Med (2018) 10. A dominant-negative version of KASH3 is described e.g. in Stewart-Hutchinson et al. Exp Cell Res. (2008) 314(8):1892-905. A dominant-negative version of KASH4 is described e.g. in Roux et al. Proc. Natl. Acad. Sci. U.S.A. (2009) 106: 2194-2199. A dominant-negative version of KASH5 is described e.g. in Horn etal. J Cell Biol (2013) 202: 1023-1039. In some embodiments, a peptide / polypeptide LINC complex inhibitor is based on a SUN domaincontaining protein (e.g. a SUN domain containing-protein as described herein). In some embodiments the peptide / polypeptide LINC complex inhibitor is a decoy / dominant-negative version of a SUN domain-containing protein. LINC complex inhibitors based on a SUN domain-containing protein may display binding to a KASH domain-containing protein (e.g. a KASH domain-containing protein as described herein), but lacks or displays a reduced level of one or more other properties of the SUN domain-containing protein on which it is based (e.g. binding to a SUN domain-containing protein, nucleoplasmic protein, lamin, and / or chromatin-binding protein). LINC complex inhibitors based on a SUN domain-containing protein may display binding to a SUN domain-containing protein (e.g. a SUN domain-containing protein as described herein), but lacks or displays a reduced level of one or more other properties of the SUN domain-containing protein on which it is based (e.g. binding to a KASH domain-containing protein, nucleoplasmic protein, lamin, and / or chromatin-binding protein). LINC complex inhibitors based on a SUN domain-containing protein preferably comprise a SUN domain. In some embodiments a LINC complex consists of, or consists essentially of, a SUN domain. The peptide / polypeptide may lack amino acid sequence(s) of a SUN domain-containing protein constituting protein domains other than a SUN domain. The peptide / polypeptide preferably lacks properties of an endogenous SUN domain-containing protein other than properties mediated by the SUN domain. The peptide / polypeptide may behave as a dominant-negative peptide / polypeptide, capable of inhibiting interaction between an endogenous SUN domain-containing protein and an endogenous interaction partner for a SUN domain-containing protein. In some embodiments, a LINC complex inhibitor comprises, or consists of, the SUN domain of SUN1, SUN2, SUN3, SUN5, SPAG4 or SUCO, or a SUN domain having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the SUN domain of SUN1, SUN2, SUN3, SUN5, SPAG4 or SUCO. In some embodiments, a LINC complex inhibitor comprises, or consists of, the amino acid sequence shown in SEQ ID NO:82, 83, 84, 85, 86 or 87, or an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence shown in SEQ ID NO:82, 83, 84, 85, 86 or 87. In some embodiments a LINC complex inhibitor lacks the full amino acid sequence of SUN1, SUN2, SUN3, SUN5, SPAG4 or SUCO. In some embodiments a LINC complex inhibitor lacks the amino acid sequence according to SEQ ID NO:88, 89, 90, 91,92 or 93. In some embodiments a LINC complex inhibitor lacks the amino acid sequence of a SUN domaincontaining protein required for binding to a nucleoplasmic protein, a lamin, and / or a chromatin-binding protein. In some embodiments a LINC complex inhibitor lacks the amino acid sequence according to SEQ ID NO:94, 95 or 96. In some embodiments, a peptide / polypeptide LINC complex inhibitor is based on a KASH domaincontaining protein (e.g. a KASH domain containing-protein as described herein). In some embodiments the peptide / polypeptide LINC complex inhibitor is a decoy / dominant-negative version of a KASH domain-containing protein. LINC complex inhibitors based on a KASH domain-containing protein may display binding to a SUN domain-containing protein (e.g. a SUN domain-containing protein as described herein), but lacks or displays a reduced level of one or more other properties of the KASH domain-containing protein on which it is based (e.g. binding to a KASH domain-containing protein, cytoplasmic protein, cytoskeletal protein, microfilament, actin, microtubule, tubulin, microtubule motor, or intermediate filament protein). LINC complex inhibitors based on a KASH domain-containing protein may display binding to a KASH domain-containing protein (e.g. a KASH domain-containing protein as described herein), but lacks or displays a reduced level of one or more other properties of the KASH domain-containing protein on which it is based (e.g. binding to a SUN domain-containing protein, cytoplasmic protein, cytoskeletal protein, microfilament, actin, microtubule, tubulin, microtubule motor, or intermediate filament protein). LINC complex inhibitors based on a KASH domain-containing protein preferably comprise a KASH domain. In some embodiments a LINC complex consists of, or consists essentially of, a KASH domain. The peptide / polypeptide may lack amino acid sequence(s) of a KASH domain-containing protein constituting protein domains other than a KASH domain. The peptide / polypeptide preferably lacks properties of an endogenous KASH domain-containing protein other than properties mediated by the KASH domain. The peptide / polypeptide may behave as a dominant-negative peptide / polypeptide, capable of inhibiting interaction between an endogenous KASH domaincontaining protein and an endogenous interaction partner for a KASH domain-containing protein. In some embodiments, a LINC complex inhibitor comprises, or consists of, the KASH domain of Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, KASH5, LRMP or a KASH domain having at least 70%, 24 preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the KASH domain of Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, KASH5 or LRMP. In some embodiments, a LINC complex inhibitor comprises, or consists of, the amino acid sequence shown in SEQ ID NO:97, 98, 99, 100, 101 or 114, or an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence shown in SEQ ID NO:97, 98, 99, 100, 101 or114. In some embodiments a LINC complex inhibitor lacks the full amino acid sequence of Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, KASH5 or LRMP. In some embodiments a LINC complex inhibitor lacks the amino acid sequence according to SEQ ID NO:102, 103, 104, 105, 106 or 113. In some embodiments a LINC complex inhibitor lacks the amino acid sequence of a KASH domaincontaining protein required for binding to a cytoplasmic protein, a cytoskeletal protein, a microfilament, actin, a microtubule, tubulin, a microtubule motor, or an intermediate filament protein. In some embodiments a LINC complex inhibitor lacks the amino acid sequence according to SEQ ID NQ:107 or 108. In some embodiments, peptide / polypeptide LINC complex inhibitors capable of binding to a LINC complex / LINC complex protein / interaction partner for a LINC complex protein and inhibiting interaction between a LINC complex protein and an interaction partner for a LINC complex protein and / or LINC complex function include e.g. peptide aptamers, thioredoxins, monobodies, anticalin, Kunitz domains, avimers, knottins, fynomers, atrimers, DARPins, affibodies, nanobodies (i.e. singledomain antibodies (sdAbs)) affilins, armadillo repeat proteins (ArmRPs), OBodies and fibronectin -reviewed e.g. in Reverdatto et al., Curr Top Med Chern. 2015; 15(12): 1082-1101, which is hereby incorporated by reference in its entirety (see also e.g. Boersma et al., J Biol Chern (2011) 286:4127385 and Emanuel et al., Mabs (2011) 3:38-48). Further peptide / polypeptide LINC complex inhibitors contemplated in connection with the present invention include antibodies (immunoglobulins) such as monoclonal antibodies, polyclonal antibodies, monospecific antibodies, multispecific antibodies (e.g., bispecific antibodies), and fragments and derivatives thereof (e.g. Fv, scFv, Fab, scFab, F(ab’)2, Fab2, diabodies, triabodies, scFv-Fc, minibodies, single domain antibodies (e.g. VhH), etc.). Such peptide / polypeptide LINC complex inhibitors can be identified by screening of libraries of the relevant peptides / polypeptides for LINC complex inhibition. Peptide / polypeptide LINC complex inhibitors may comprise further amino acids or sequences of amino acids. For example, the peptides / polypeptides may comprise amino acid sequence(s) to facilitate expression, folding, trafficking, processing, purification or detection. For example, the peptide / polypeptide may comprise a sequence encoding a His, (e.g. 6XHis), Myc, GST, MBP, FLAG, HA, E, or Biotin tag, optionally at the N- or C- terminus of the antigen-binding molecule / polypeptide. In 25 some embodiments the peptide / polypeptide comprises a detectable moiety, e.g. a fluorescent, lunminescent, immuno-detectable, radio, chemical, nucleic acid or enzymatic label. In some embodiments, peptides / polypeptides may comprise an N-terminal signal sequence, a signal peptidase cleavage site, and a C-terminal targeting peptide sequence. The peptides / polypeptides may additionally comprise a signal peptide (also known as a leader sequence or signal sequence). Signal peptides normally consist of a sequence of 5-30 hydrophobic amino acids, which form a single alpha helix. Secreted proteins and proteins expressed at the cell surface often comprise signal peptides. The signal peptide may be present at the N-terminus of the peptide / polypeptide, and may be present in the newly synthesised peptide / polypeptide. Signal peptides are often removed by cleavage, and thus are not comprised in the mature peptide / polypeptide. In some embodiments an N-terminal signal sequence is derived from a secretory protein or a Type I transmembrane protein. In some embodiments the secretory protein or Type I transmembrane protein is selected from: human serum albumin, proinsulin, transferrin receptor, EGF receptor, pre-pro-opiomelanocortin, carboxypeptidases, complement proteins, fibrinogen, cytokines, chemokines, , fibrinogen, pancreatic digestive enzymes (for example, proteases, amylases and lipases), endoplasmic reticulum lumenal proteins, for example protein disulphide isomerases and GRP94. In some embodiments the N-terminal signal sequence is derived from human serum albumin. In some embodiments the N-terminal signal sequence is not preceded at its N-terminus by any other tags. In some embodiments the peptide / polypeptide comprises a signal peptidase cleavage site. In some embodiments the signal peptidase cleavage site is a signal peptidase cleavage site derived from or is one of: human serum albumin, proinsulin, transferrin receptor, EGF receptor, pre-pro-opiomelanocortin, pancreatic digestive enzymes (for example, proteases, amylases and lipases), endoplasmic reticulum lumenal proteins, such as protein disulphide isomerases and GRP94. In some embodiments the signal peptidase cleavage site is derived from human serum albumin. In some embodiments the peptide / polypeptide comprises a sequence for targeted intracellular trafficking of the peptide / polypeptide to the nuclear envelope. In some embodiments the peptide / polypeptide comprises an endoplasmic-reticulum (ER) retention motif. Suitable endoplasmic-reticulum retention sequences are known in the art. In some embodiments the ER retention motif is a KDEL sequence. A KDEL sequence KDEL or a variant thereof that works to retain a protein in the endoplasmic-reticulum. KDEL variants may comprise or consist of the prosite motif [KRHQSA]-[DENQ]-E-L (described in Hulo et al., 2006, Nucleic acids research 34: D227-D230), or a variant described by in Raykhel et al., 2007 (J. Cell Biol. 179(6):1193-1204) who proposed an expanded prosite motif definition. Raykhel demonstrated endoplasmic retention with variants in which the 4 position (i.e. the K position) included F, WY as an alternative to KRHQSA, a range of 3 position (i.e. the D position) residues that extended far beyond DENQ, F or M in the 1 position (the L position), and D in the 2 position (i.e. the E position). For example, the KDEL motif may be CDEL, KCEL or HVEL as proposed by Raykhel et al. Thus, in some aspects disclosed herein the endoplasmic-reticulum (ER) retention motif is KDEL or a variant thereof which exhibitis ER retention activity. In some embodiments the peptide / polypeptide comprises a C-terminal targeting peptide sequence. In some embodiments the C-terminal targeting peptide sequence prevents secretion of the peptide / polypeptide. In some embodiments, the C-terminal targeting peptide sequence is a KDEL tetrapeptide Golgi retrieval sequence. Examples of such structures are shown in Figures 11 and 12. In some embodiments the peptide / polypeptide comprises an epitope tag. In some embodiments the epitope tag is N-terminal, or located anywhere in the peptide / polypeptide downstream of (after) the C-terminal targeting peptide sequence [for example an endoplasmi-reticulum retention motif such as a KDEL sequence], or located anywhere in the peptide / polypeptide except upstream of (before) the N-terminal signal sequence. In some embodiments, the epitope tag is selected from: cellulose binding domain (CBD), chloramphenicol acetyl transferase (CAT), dihydrofolate reductase (DHFR), one or more FLAG tags, glutathione S-transferase (GST), green fluorescent protein (GFP), haemagglutinin A (HA), histidine (His), Herpes simplex virus (HSV), luciferase, maltose-binding protein (MBP), c-Myc, Protein A, Protein G, streptavidin, T7, thioredoxin, V5, vesicular stomatitis virus glycoprotein (VSV-G), and combinations thereof. In some embodiments the epitope tag is haemagglutinin A (HA). In some embodiments, a peptide / polypeptide comprises a signal sequence (i.e. prior to cleavage to remove the signal sequence), a humanized SunlDN sequence and a KDEL sequence (e.g. as encoded by SEQ ID NO:4). In some embodiments, a peptide / polypeptide comprises a signal sequence, a humanized Sun2DN sequence and a KDEL sequence (e.g. as encoded by SEQ ID NO:5). For SUN domain constructs it is expected that the SUN domain (crystal structure solved by the Kutay and Schwartz labs [Sosa et al., Cell 149(5):1035-47 (2012)] and an additional upstream 20 amino acid residues corresponding to the alpha-3 region of coiled-coil-2, is sufficient to disrupt the SUN-KASH interaction as it is capable of binding to the KASH domain [Jahed et al., Biophysical Journal 114 (5): 1190-1203 (2018)]. This is instead of the entire lumenal domain (coiled-coil domain and SUN domain). The human SUN1 SUN domain nucleic acid sequence is set forth in SEQ ID NO:80. The presence of the signal sequence and a KDEL sequence may be important for targeting to the perinuclear space. In some embodiments, a LINC complex inhibitor comprises, or consists of, the amino acid sequence shown in SEQ ID NO:115, or an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence shown in SEQ ID NO:115. In some embodiments, a LINC complex 27 inhibitor comprises, or consists of, the amino acid sequence shown in SEQ ID NO:116, or an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence shown in SEQ ID NO:116. In some embodiments peptides / polypeptides comprise either the lumenal domain of a SUN domaincontaining protein, or the SUN domain of a SUN domain-containing protein. In some embodiments the lumenal domain of Sun1 comprises amino acids 458-913 of full-length mouse Sun1 (UniProt: Q9D666) or its human equivalent comprising the coiled coil domain and the SUN domain and lacking the transmembrane domain. A schematic of the structure of a dominant negative form of Sun1 is shown in Figure 7. In some embodiments the peptides / polypeptides comprise a humanized SunlDN sequence or a humanized Sun2DN sequence. Rather than expressing components of a lumenal domain of a SUN domain-containing protein, a KASH domain may be expressed to disrupt a LINC complex by competing with endogenous Nesprins (which comprise a KASH domain) for binding to SUN1 and SUN2 domains. Accordingly, in some embodiments the peptides / polypeptides comprise a KASH domain, and an N-terminal stabiliser polypeptide sequence. In some embodiments the peptide / polypeptide comprises a KASH domain comprising a transmembrane domain and a SUN-interacting peptide. In some embodiments the peptide / polypeptide comprises a KASH domain that traverses the outer nuclear membrane, a SUNinteracting KASH peptide that extends into the perinuclear space at the C-terminus, and an N-terminal stabiliser polypeptide sequence in the cytoplasm. It will be understood that KASH domain constructs with extensions after the last C-terminal amino acid of the naturally occurring KASH domain are not expected to work i.e. C-terminal tags, or even an additional carboxy-terminal single amino acid, will disrupt KASH interaction with SUN. In some embodiments, the KASH domain is selected from the group consisting of KASH1 (derived from Nesprin-1 (SYNE1 gene)), KASH2 (derived from Nesprin-2 (SYNE2 gene)), KASH3 (derived from Nesprin-3 (SYNE3 gene)), KASH4 (derived from Nesprin-4 (SYNE4 gene)) and KASH5 (derived from KASH5 / CCDC155 (KASH5 gene)). In some embodiments the KASH 1 domain comprises the human amino acid sequence set forth in SEQ ID NO:7; the KASH 2 domain comprises the human amino acid sequence set forth in SEQ ID NO:9; the KASH 3 domain comprises the human amino acid sequence set forth in SEQ ID NO:11; the KASH 4 domain comprises the human amino acid sequence set forth in SEQ ID NO:13; and the KASH 5 domain comprises the human amino acid sequence set forth in SEQ ID NO:15. An alignment of the five KASH amino acid sequences is shown in Figure 14. In some embodiments the KASH domain nucleic acid sequence has at least 80%, at least 85%, at least 90%, at least 95% sequence identity or 100% sequence identity to the nucleic acid sequence of the KASH1 domain set forth in SEQ ID NO:6; the nucleic acid sequence of the KASH2 domain set forth in SEQ ID NO:8; the nucleic acid sequence of the KASH3 domain set forth in SEQ ID NO:10; the nucleic acid sequence of the KASH4 domain set forth in SEQ ID NO:12; or the nucleic acid sequence of the KASH5 domain set forth in SEQ ID NO:14. In some embodiments, e.g. for the purposes of clinical use, the KASH domain is the human KASH1 domain of SYNE1 having at least 80%, at least 85%, at least 90%, at least 95% sequence identity or 100% sequence identity to the nucleic acid sequence of the human KASH1 domain set forth in SEQ ID NO:6. In some embodiments, the KASH domain does not comprise any extensions after the last C-terminal amino acid compared to a naturally occurring KASH domain. In some embodiments an N-terminal stabiliser polypeptide sequence is selected from the group consisting of green fluorescent protein (GFP), cellulose binding domain (CBD), chloramphenicol acetyl transferase (CAT), dihydrofolate reductase (DHFR), glutathione S-transferase (GST), luciferase, maltose-binding protein (MBP), Protein A, Protein G, streptavidin, thioredoxin, DHFR, including multiples and combinations thereof. In some embodiments, the N-terminal stabiliser polypeptide sequence forms a discretely folded domain. In some embodiments, the peptide / polypeptide comprises a KASH domain, and an N-terminal stabiliser polypeptide sequence, wherein the KASH domain is selected from the group comprising KASH1, KASH2, KASH3, KASH4 and KASH5. In some embodiments, the N-terminal stabiliser polypeptide sequence is green fluorescent protein (GFP). In some embodiments a LINC complex inhibitor is a small molecule inhibitor of a LINC complex. As used herein, a “small molecule” refers to a low molecular weight (< 1000 daltons, typically between ~300-700 daltons) organic compound. A small molecule LINC complex inhibitor may bind to a LINC complex, a LINC complex protein, or an interaction partner for a LINC complex protein. A small molecule inhibitor LINC complex inhibitor may 29 inhibit interaction between a LINC complex protein and an interaction partner for a LINC complex protein. A small molecule inhibitor LINC complex inhibitor may bind to a LINC complex and inhibit LINC complex function. Suitable small molecule LINC complex inhibitors may be identified e.g. by screening of small molecule libraries, e.g. as described in Example 7 herein. In some embodiments a LINC complex inhibitor is, or comprises, a nucleic acid. The nucleic acid may bind to a LINC complex, a LINC complex protein, or an interaction partner for a LINC complex protein. The nucleic acid may inhibit interaction between a LINC complex protein and an interaction partner for a LINC complex protein. The nucleic acid may bind to a LINC complex and inhibit LINC complex function. Nucleic acid aptamers are reviewed e.g. in Zhou and Rossi Nat Rev Drug Discov. 2017 16(3):181 -202. They may be identified and / or produced by the method of Systematic Evolution of Ligands by Exponential enrichment (SELEX), or by developing SOMAmers (slow off-rate modified aptamers) (Gold L et al. (2010) PLoS ONE 5(12):e15004). Aptamers and SELEX are described in Tuerk and Gold, Science (1990) 249(4968):505-10, and in WO 91 / 19813. Nucleic acid aptamers may comprise DNA and / or RNA, and may be single-stranded or doublestranded. They may comprise chemically modified nucleic acids, for example in which the sugar and / or phosphate and / or base is chemically modified. Such modifications may improve the stability of the aptamer or make the aptamer more resistant to degradation and may include modification at the 2' position of ribose. Nucleic acid aptamers may be chemically synthesised, e.g. on a solid support. Solid phase synthesis may use phosphoramidite chemistry. Briefly, a solid supported nucleotide is detritylated, then coupled with a suitably activated nucleoside phosphoramidite to form a phosphite triester linkage. Capping may then occur, followed by oxidation of the phosphite triester with an oxidant, typically iodine. The cycle may then be repeated to assemble the aptamer (e.g., see Sinha, N. D.; Biernat, J.; McManus, J.; Koster, H. Nucleic Acids Res. 1984, 12, 4539; and Beaucage, S. L.; Lyer, R. P. (1992). Tetrahedron 48 (12):2223). In some embodiments, a LINC complex inhibitor capable of reducing expression (e.g. gene and / or protein expression) of a LINC complex protein. In some embodiments the LINC complex inhibitor reduces or prevents the expression of an endogenous LINC complex protein. Inhibition of expression of a LINC complex protein will result in a decrease in the quantity of a LINC complex protein and / or the quantity of LINC complexes comprising the constituent protein in a 30 cell / tissue / organ / organ system / subject. For example, in a given cell the inhibition of expression of a LINC complex protein will result in a decrease in the level of a LINC complex protein and / or of LINC complexes comprising the constituent protein relative to an untreated cell. Inhibition may be partial. Preferred degrees of inhibition are at least 50%, more preferably one of at least 60%, 70%, 80%, 85% or 90%. A level of inhibition between 90% and 100% is considered a ‘silencing’ of expression or function. Gene and protein expression may be determined as described herein or by methods in the art that are well known to a skilled person. In some embodiments a LINC complex inhibitor reduces or prevents the expression of SUN1, SUN2, SUN3, SUN5, SPAG4 or SUCO. In some embodiments a LINC complex inhibitor reduces or prevents the expression of SUN1 or SUN2. In some embodiments a LINC complex inhibitor reduces or prevents the expression of a polypeptide according to SEQ ID NO:82, 83, 84, 85, 86 or 87. In some embodiments a LINC complex inhibitor reduces or prevents the expression of a polypeptide according to SEQ ID NO:82 or 83. In some embodiments a LINC complex inhibitor reduces or prevents the expression of Nesprin-1, Nesprin-2, Nesprin-3, Nesprin-4, KASH5 or LRMP. In some embodiments a LINC complex inhibitor reduces or prevents the expression of a polypeptide according to SEQ ID NO: 102, 103, 104, 105, 106 or 113. In some embodiments a LINC complex inhibitor reduces or prevents the expression of Nesprin-1, Nesprin-2 or Nesprin-3 In some embodiments a LINC complex inhibitor reduces or prevents the expression of a polypeptide according to SEQ ID NO: 102, 103 or 104. In some embodiments, a LINC complex inhibitor may target a particular domain / region of a LINC complex protein. In some embodiments the LINC complex inhibitor reduces or prevents the expression of an isoform of a LINC complex protein comprising one or more domains / regions of interest. For example, a domain or region of interest may be or comprise: a SUN domain, a KASH domain and / or a domain required for interaction with an interaction partner for the LINC complex protein. For example, a domain or region of interest may be required for interaction with a KASH domaincontaining protein, a SUN domain-containing protein, a nucleoplasmic protein, a lamin, a chromatinbinding protein, a cytoplasmic protein, a cytoskeletal protein, a microfilament, actin, a microtubule, tubulin, a microtubule motor and / or an intermediate filament protein. In some embodiments, a LINC complex inhibitor may alter splicing of pre-mRNA encoding the LINC complex protein to increase the proportion of mature mRNA encoding isoform(s) lacking the relevant domains / regions, and / or to decrease the proportion of mature mRNA encoding isoform(s) comprising the relevant domains / regions. 31 In some embodiments, a LINC complex inhibitor may modify nucleic acid encoding the LINC complex protein to increase expression of isoform(s) lacking the relevant domains / regions, and / or may modify the nucleic acid encoding the LINC complex protein to decrease expression of isoform(s) comprising the relevant domains / regions of the protein. In some embodiments the LINC complex inhibitor is an inhibitory nucleic acid. In some embodiments, the inhibitory nucleic acid is an antisense nucleic acid. In some embodiments the inhibitory nucleic acid is an antisense oligonucleotide (ASO). Antisense oligonucleotides may be single-stranded, and may bind by complementary sequence binding to a target oligonucleotide, e.g. mRNA. ASOs may be designed to inhibit / prevent expression of a LINC complex protein or particular isoforms thereof. Oligonucleotides designed to inhibit / prevent expression of a LINC complex protein, or particular isoforms thereof, may have substantial sequence identity to a portion of nucleic acid encoding the LINC complex protein / the relevant isoform, or the complementary sequence thereto. In some embodiments, the inhibitory nucleic acid reduces expression of a LINC complex protein by RNA interference (RNAi). RNAi involves inhibition of gene expression and translation by targeted neutralisation of mRNA molecules. In some embodiments, the inhibitory nucleic acid is a small interfering RNA (siRNA), a short hairpin RNA (shRNA), ora micro RNA (miRNA). A role for the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci has been demonstrated. Double-stranded RNA (dsRNA)-dependent post transcriptional silencing, also known as RNA interference (RNAi), is a phenomenon in which dsRNA complexes can target specific genes of homology for silencing in a short period of time. It acts as a signal to promote degradation of mRNA with sequence identity. A 20nt siRNA is generally long enough to induce gene-specific silencing, but short enough to evade host response. The decrease in expression of targeted gene products can be extensive with 90% silencing induced by a few molecules of siRNA. RNAi based therapeutics have been progressed into Phase I, II and III clinical trials for a number of indications (Nature 2009 Jan 22; 457(7228):426-433). In the art, such RNA sequences are termed "short or small interfering RNAs" (siRNAs) or "microRNAs" (miRNAs) depending on their origin. Both types of sequence may be used to down-regulate gene expression by binding to complementary RNAs and either triggering mRNA elimination (RNAi) or arresting mRNA translation into protein. siRNA are derived by processing of long double stranded RNAs and when found in nature are typically of exogenous origin. Micro-interfering RNAs (miRNA) are endogenously encoded small non-coding RNAs, derived by processing of short hairpins. Both siRNA and miRNA can inhibit the translation of mRNAs bearing partially complimentary target sequences without RNA cleavage and degrade mRNAs bearing fully complementary sequences. siRNAs are typically double stranded and, in order to optimise the effectiveness of RNA mediated down-regulation of the function of a target gene, it is preferred that the length of the siRNA molecule is chosen to ensure correct recognition of the siRNA by the RISC complex that mediates the recognition by the siRNA of the mRNA target and so that the siRNA is short enough to reduce a host response. miRNAs are typically single stranded and have regions that are partially complementary enabling the ligands to form a hairpin. miRNAs are RNA genes which are transcribed from DNA, but are not translated into protein. A DNA sequence that codes for a miRNA gene is longer than the miRNA. This DNA sequence includes the miRNA sequence and an approximate reverse complement. When this DNA sequence is transcribed into a single-stranded RNA molecule, the miRNA sequence and its reverse-complement base pair to form a partially double stranded RNA segment. The design of microRNA sequences is discussed e.g. in John et al, PLoS Biology, 11(2), 1862-1879, 2004. Typically, the oligonucleotides intended to mimic the effects of siRNA or miRNA have between 10 and 40 ribonucleotides (or synthetic analogues thereof), more preferably between 17 and 30 ribonucleotides, more preferably between 19 and 25 ribonucleotides and most preferably between 21 and 23 ribonucleotides. In some embodiments of the invention employing double-stranded siRNA, the molecule may have symmetric 3' overhangs, e.g. of one or two (ribo)nucleotides, typically a UU of dTdT 3' overhang. Based on the disclosure provided herein, the skilled person can readily design suitable siRNA and miRNA sequences, for example using resources such the Ambion siRNA finder. siRNA and miRNA sequences can be synthetically produced and added exogenously to cause gene downregulation or produced using expression systems (e.g. vectors). In some embodiments the siRNA is synthesized synthetically. siRNA-mediated knockdown of LINC complex proteins and siRNAs for achieving the same are described e.g. in Ostlund et al., Journal of Cell Science (2009) 122:4099-4108, Hatch and Hetzer, J Cell Biol. (2016) 215(1):27-36, Matsumoto etal., Nucleus. (2016) 7(1):68-83, Uzeretal., Stem Cells. (2015) 33(6):2063-76, Thakaretal., Mol Biol Cell. (2017) 28(1): 182-191, Espigat-Georger et al., J Cell Sci. (2016) 129(22):4227-4237, Yang etal., Int J Mol Med. (2013) 32(4):805-12, Rajgoretal., PLoS One. 2012;7(7):e40098, Zhang et al., Exp Cell Res. (2016) 345(2):168-179, Warren et al. J Biol Chern. (2010) 285(2):1311-20 and King etal., Cytoskeleton (Hoboken) (2014) 71(7):423-34, which are hereby incorporated by reference in their entirety. Longer double stranded RNAs may be processed in the cell to produce siRNAs (see for example Myers (2003) Nature Biotechnology 21:324-328). The longer dsRNA molecule may have symmetric 3' or 5' overhangs, e.g. of one or two (ribo)nucleotides, or may have blunt ends. The longer dsRNA 33 molecules may be 25 nucleotides or longer. Preferably, the longer dsRNA molecules are between 25 and 30 nucleotides long. More preferably, the longer dsRNA molecules are between 25 and 27 nucleotides long. Most preferably, the longer dsRNA molecules are 27 nucleotides in length. dsRNAs 30 nucleotides or more in length may be expressed using the vector pDECAP (Shinagawa et al., Genes and Dev., 17, 1340-5, 2003). Another alternative is the expression of a short hairpin RNA molecule (shRNA) in the cell. shRNAs are more stable than synthetic siRNAs. A shRNA consists of short inverted repeats separated by a small loop sequence. One inverted repeat is complimentary to the gene target. In the cell the shRNA is processed by DICER into a siRNA which degrades the target gene mRNA and suppresses expression. In some embodiments the shRNA is produced within a cell by transcription from a vector. shRNAs may be produced within a cell by transfecting the cell with a vector encoding the shRNA sequence under control of a RNA polymerase III promoter such as the human H1 or 7SK promoter or a RNA polymerase II promoter. Alternatively, the shRNA may be synthesised exogenously (in vitro) by transcription from a vector. The shRNA may then be introduced directly into the cell. Preferably, the shRNA molecule comprises a partial sequence of a gene encoding a LINC complex protein. Preferably, the shRNA sequence is between 40 and 100 bases in length, more preferably between 40 and 70 bases in length. The stem of the hairpin is preferably between 19 and 30 base pairs in length. The stem may contain G-U pairings to stabilise the hairpin structure. shRNA-mediated knockdown of LINC complex proteins and shRNAs for achieving the same are described e.g. in Kelkar et al., Nucleus. (2015) 6(6): 479-489, MroB et al., Nucleus. (2018) 9(1): 503515, Xing et al., International Journal of Cell Biology (2017) Article ID: 8607532, Arsenovic et al., Biophys J. (2016) 110(1):34-43 and Li et al., Scientific Reports (2017) 7: Article number: 9157, which are hereby incorporated by reference in their entirety. In some embodiments, the inhibitory nucleic acid is a splice-switching oligonucleotide (SSO). Splice switching oligonucleotides are reviewed e.g. in Haves and Hastings, Nucleic Acids Res. (2016) 44(14): 6549-6563, which is hereby incorporated by reference in its entirety. SSOs disrupt the normal splicing of target RNA transcripts by blocking the RNA-RNA base-pairing and / or protein-RNA binding interactions that occur between components of the splicing machinery and pre-mRNA. SSOs may be employed to alter the number / proportion of mature mRNA transcripts encoding a LINC complex protein or particular isoform(s) thereof. SSOs may be designed to target a specific region of the target transcript, e.g. to effect skipping of exon(s) of interest, e.g. exons encoding domains / regions of interest. SSOs generally comprise alterations to oligonucleotide sugar-phosphate backbones to prevent RNAse H degradation, and may comprise include e.g. phosphorodiamidate morpholino (PMOs), peptide nucleic acid (PNA), locked nucleic acid (LNA), and / or 2'O-methyl (2'OMe) and 2'-O-methoxyethyl (MOE) ribose modifications. 34 Inhibitory nucleic acids may be made recombinantly by transcription of a nucleic acid sequence, e.g. contained within vector. Transcription may be performed in cell-free transcription reactions, or in a cell comprising nucleic acid encoding the inhibitory nucleic acid. In some embodiments inhibitory nucleic acids are produced within a cell, e.g. by transcription from a vector. Vectors encoding such molecules may be introduced into cells in any of the ways known in the art. Optionally, expression of the nucleic acid can be regulated using a cell / tissue (e.g. heart, muscle, etc.) specific promoter. Inhibitory nucleic acids may also be synthesized using standard solid or solution phase synthesis techniques which are known in the art. In some embodiments, the LINC complex inhibitor is a molecule / plurality of molecules capable of modifying nucleic acid encoding a LINC complex protein to reduce / prevent expression of a LINC complex protein or particular isoform(s) thereof. Modifying nucleic acid encoding a LINC complex protein may comprise modifying a gene encoding a LINC complex protein. In some embodiments, modifying nucleic acid encoding a LINC complex protein comprises introducing an insertion, substitution or deletion into a nucleic acid sequence encoding the LINC complex protein. In some embodiments modifying nucleic acid encoding a LINC complex protein comprises modifying the nucleic acid to introduce a premature stop codon in the sequence transcribed from the nucleic acid. In some embodiments modifying nucleic acid encoding a LINC complex protein comprises modifying the nucleic acid to encode a truncated and / or non-functional version of the LINC complex protein. In some embodiments modifying nucleic acid encoding a LINC complex protein comprises modifying the nucleic acid to encode a version of the LINC complex protein which is misfolded and / or degraded. The modification may be of nucleic acid comprised in a cell, e.g. endogenous nucleic acid encoding a LINC complex protein. The modification causes the cell to have a reduced level of gene and / or protein expression of a LINC complex protein or particular isoform(s) thereof as compared to an equivalent unmodified cell. In some embodiments, modification may be to a region of the nucleic acid encoding a LINC complex protein involved in (e.g. required for) LINC complex formation. For example, in some embodiments modification may target a region of a gene encoding a SUN domain-containing protein encoding a encoding a SUN domain. In some embodiments modification may target a region of a gene encoding a KASH domain-containing protein encoding a encoding a KASH domain. In some embodiments the modification is performed in vitro or ex vivo. In some embodiments the modification is performed in vivo. Methods for modifying nucleic acids encoding proteins of interest and agents for achieving the same are well known in the art, and include e.g. including modification of the target nucleic acid by homologous recombination, and target nucleic acid editing using site-specific nucleases (SSNs). For example, the inventors demonstrate CRISPR / Cas9-mediated disruption ofSun1 and Nesprin-1 in the experimental examples herein. Suitable methods may employ targeting by homologous recombination, which is reviewed, for example, in Mortensen Curr Protoc Neurosci. (2007) Chapter 4:Unit 4.29 and Vasquez et al., PNAS 2001,98(15): 8403-8410 both of which are hereby incorporated by reference in their entirety. Targeting by homologous recombination involves the exchange of nucleic acid sequence through crossover events guided by homologous sequences. In some embodiments the methods employ target nucleic acid editing using SSNs. Gene editing using SSNs is reviewed e.g. in Eid and Mahfouz, Exp Mol Med. 2016 Oct; 48(10): e265, which is hereby incorporated by reference in its entirety. Enzymes capable of creating site-specific double strand breaks (DSBs) can be engineered to introduce DSBs to target nucleic acid sequence(s) of interest. DSBs may be repaired by either error-prone non-homologous end-joining (NHEJ), in which the two ends of the break are rejoined, often with insertion or deletion of nucleotides. Alternatively DSBs may be repaired by highly homology-directed repair (HDR), in which a DNA template with ends homologous to the break site is supplied and introduced at the site of the DSB. SSNs capable of being engineered to generate target nucleic acid sequence-specific DSBs include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced palindromic repeats / CRISPR-associated-9 (CRISPR / Cas9) systems. ZFN systems are reviewed e.g. in Umov etal., Nat Rev Genet. (2010) 11(9):636-46, which is hereby incorporated by reference in its entirety. ZFNs comprise a programmable Zinc Finger DNA-binding domain and a DNA-cleaving domain (e.g. a Fok\ endonuclease domain). The DNA-binding domain may be identified by screening a Zinc Finger array capable of binding to the target nucleic acid sequence. TALEN systems are reviewed e.g. in Mahfouz et al., Plant Biotechnol J. (2014) 12(8):1006-14, which is hereby incorporated by reference in its entirety. TALENs comprise a programmable DNA-binding TALE domain and a DNA-cleaving domain (e.g. a Fok\ endonuclease domain). TALEs comprise repeat domains consisting of repeats of 33-39 amino acids, which are identical except for two residues at positions 12 and 13 of each repeat which are repeat variable di-residues (RVDs). Each RVD determines binding of the repeat to a nucleotide in the target DNA sequence according to the following relationship: “HD” binds to C, “Nl” binds to A, “NG” binds to T and “NN” or “NK” binds to G (Moscou and Bogdanove, Science (2009) 326(5959):1501.). CRISPR / Cas9 and related systems e.g. CRISPR / Cpf1, CRISPR / C2c1, CRISPR / C2c2 and CRISPR / C2c3 are reviewed e.g. in Nakade et al., Bioengineered (2017) 8(3):265-273, which is hereby incorporated by reference in its entirety. These systems comprise an endonuclease (e.g. Cas9, Cpf1 etc.) and the single-guide RNA (sgRNA) molecule. The sgRNA can be engineered to target endonuclease activity to nucleic acid sequences of interest. In some embodiments, LINO complex inhibition employs a site-specific nuclease (SSN) system targeting a LINO complex protein. Accordingly in some embodiments the LINO complex inhibitor comprises or consists of SSN system targeting a LINO complex protein. In some embodiments LINO complex inhibition employs nucleic acid(s) encoding a SSN system targeting a LINO complex protein. In some embodiments, the SSN system targets a region of the nucleic acid encoding a LINO complex protein involved in (e.g. required for) LINO complex formation. For example, in some embodiments the SSN system may disrupt expression of an exon of a gene encoding a SUN domain-containing protein encoding a SUN domain. In some embodiments the SSN system may disrupt expression of an exon of a gene encoding a KASH domain-containing protein encoding a KASH domain. In particular embodiments, the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the conserved tyrosine residue. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the tyrosine at position 154 of SEQ ID NO:82. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the tyrosine at position 153 of SEQ ID NO:83. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the tyrosine at position 153 of SEQ ID NO:84. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the tyrosine at position 151 of SEQ ID NO:85. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the tyrosine at position 152 of SEQ ID NO:86. In particular embodiments, the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a SUN domain-containing protein upstream of the sequence encoding the conserved tyrosine residue. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a KASH domain-containing protein upstream of the sequence encoding the proline-rich region at the C-terminus. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a KASH domain-containing protein upstream of the sequence encoding the proline at position 57 of SEQ ID NO:97. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a KASH domain-containing protein upstream of the sequence encoding the proline at position 57 of SEQ ID NO:98. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a KASH domain-containing protein upstream of the sequence encoding the proline at position 56 of SEQ ID NO:99. In some embodiments the SSN system may introduce an insertion / deletion in the nucleic acid sequence of a gene encoding a KASH domain-containing protein upstream of the sequence encoding the proline at position 56 of SEQ ID NQ:100. In some embodiments the SSN system is a ZFN system, a TALEN system, CRISPR / Cas9 system, a CRISPR / Cpf1 system, a CRISPR / C2c1 system, a CRISPR / C2c2 system or a CRISPR / C2c3 system. In some embodiments the SSN system is a CRISPR / Cas9 system. In such embodiments, the LINC complex inhibition may employ nucleic acid(s) encoding a CRISPR RNA (crRNA) targeting nucleic acid encoding a LINC complex protein, and a trans-activating crRNA (tracrRNA) for processing the crRNA to its mature form. CRISPR / Cas9 systems for targeted disruption of LINC complex proteins SUN1 and SUN2 are described e.g. in Schaller et al., J Virol. (2017) 91(19): pii: e00463-17, which is hereby incorporated by reference in its entirety. Rather than expressing components of a lumenal domain of a SUN domain-containing protein ora KASH domain to disrupt a LINC complex by competing for binding with endogenous Nesprins (which comprise a KASH domain) or Sun1 and Sun2 (which comprise a SUN domain), another approach for disrupting the LINC complex is to modify the endogenous SUN domain or KASH domain so that it fails to bind to, or has reduced binding capacity for, its cognate LINC complex binding partner. As both the SUN domain and the KASH domain are located at the C-termini of their respective proteins, one way of producing a modified SUN or KASH domain is to use a CRISPR / Cas system to modify the genes encoding SUN or KASH domain proteins to generate a premature stop codon at the 3’ end of the respective protein sequences following CRISPR-induced non-homologous end joining. This would result in a truncated protein with its C-terminal SUN or KASH domain mutated. The 38 truncated protein would be expressed and membrane-localized, but unable to interact with its cognate LINC complex partners. Accordingly, in some embodiments a LINC complex inhibitor is a CRISPR-Cas or other synthetic nuclease system capable of modifying nucleic acid that encodes the SUN domain or KASH domain of endogenous Sun or Nesprin protein, respectively. In some embodiments the CRISPR-Cas system modifies the endogenous SUN domain or KASH domain of Sun1 or Nesprin-1 protein, respectively, to disrupt a LINC complex. The respective nucleic acids are Sun1 and Synel. In some embodiments, the CRISPR-Cas system comprises a gRNA nucleic acid sequence comprising 5’-GCACAATAGCCTCGGATGTCG-3’ (SEQ ID NO:66), capable of modifying the SUN domain of mouse Sun1. In some embodiments, the CRISPR-Cas system comprises a gRNA nucleic acid targeting the human SUN1 domain set forth in SEQ ID NO:80. In some embodiments the gRNA nucleic acid sequence targets the end of exon 20 comprising a nucleic acid sequence set forth in SEQ ID NO:81. In some embodiments the gRNA nucleic acid sequence targets a SUN1 nucleic acid sequence selected from the group comprising SEQ ID NO:55; SEQ ID NO:56; SEQ ID NO:57; SEQ ID NO:58; SEQ ID NO:59; SEQ ID NQ:60; SEQ ID NO:61; SEQ ID NO:62; SEQ ID NO:63; SEQ ID NO:64 and SEQ ID NO:65 set forth in Table 3. In some embodiments, the CRISPR-Cas system comprises a gRNA nucleic acid sequence comprising 5’-CCGTTGGTATATCTGAGCAT-3’ (SEQ ID NO:34), capable of modifying the KASH domain of mouse Syne-1. In some embodiments, the CRISPR-Cas system comprises a gRNA nucleic acid sequence targeting the human KASH domain set forth in SEQ ID NO:6. In some embodiments the gRNA nucleic acid sequence comprises a nucleic sequence selected from the group comprising SEQ ID NO:44; SEQ ID NO:45; SEQ ID NO:46; SEQ ID NO:47; SEQ ID NO:48; SEQ ID NO:49; SEQ ID NQ:50; SEQ ID NO:51; SEQ ID NO:52; SEQ ID NO:53 and SEQ ID NO:54 set forth in Table 3. In some embodiments, the CRISPR-Cas system is a CRISPR-Cas9 system or variant thereof. Administration / delivery of LINC complex inhibitors Administration of a LINC complex inhibitor to a subject in accordance with the present invention is preferably in a "therapeutically effective” or “prophylactically effective” amount, this being sufficient to show therapeutic / prophylactic benefit to the subject. The actual amount administered, and rate and time-course of administration, will depend on the nature and severity of the disease to be treated / prevented, and the nature of the LINC complex inhibitor. Prescription of treatment, e.g. decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors, and typically takes account of the disease / condition to be treated, the condition of the individual subject, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington’s Pharmaceutical Sciences, 20th Edition, 2000, pub. Lippincott, Williams & Wilkins. In therapeutic applications, LINC complex inhibitors are preferably formulated as a medicament or pharmaceutical together with one or more other pharmaceutically acceptable ingredients well known to those skilled in the art, including, but not limited to, pharmaceutically acceptable carriers, adjuvants, excipients, diluents, fillers, buffers, preservatives, anti-oxidants, lubricants, stabilisers, solubilisers, surfactants (e.g., wetting agents), masking agents, colouring agents, flavouring agents, and sweetening agents. The term "pharmaceutically acceptable" as used herein pertains to compounds, ingredients, materials, compositions, dosage forms, etc., which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of the subject in question (e.g., human) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each carrier, adjuvant, excipient, etc. must also be "acceptable" in the sense of being compatible with the other ingredients of the formulation. Suitable carriers, adjuvants, excipients, etc. can be found in standard pharmaceutical texts, for example, Remington’s Pharmaceutical Sciences, 20th Edition, 2000, pub. Lippincott, Williams & Wilkins; and Handbook of Pharmaceutical Excipients, 2nd edition, 1994. The formulations may be prepared by any methods well known in the art of pharmacy. Such methods include the step of bringing into association the active compound with a carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active compound with carriers (e.g., liquid carriers, finely divided solid carrier, etc.), and then shaping the product, if necessary. The formulations may be prepared for topical, parenteral, systemic, intravenous, intra-arterial, intramuscular, intrathecal, intraocular, intra-conjunctival, subcutaneous, oral ortransdermal routes of administration which may include injection. Injectable formulations may comprise the selected agent in a sterile or isotonic medium. The formulation and mode of administration may be selected according to the agent to be administered, and disease to be treated / prevented. Administration of a LINC complex inhibitor preferably results in modification of a cell or cells to comprise a LINC complex inhibitor as described herein. LINC complex inhibitors may be formulated to facilitate delivery to and / or uptake by a cell / tissue. LINC complex inhibitors may be linked to a moiety in order to facilitate delivery to and / or uptake by a cell / tissue. Strategies for facilitating intracellular delivery of molecular cargo are reviewed e.g. in Li et al., Int. J. Mol. Sci. (2015) 16: 19518-19536 and Fu et al., Bioconjug Chern. (2014) 25(9): 1602-1608, which are hereby incorporated by reference in their entirety. In some embodiments a LINC complex inhibitor is formulated with a cationic polymer. In some embodiments a LINC complex inhibitor is encapsulated in a nanoparticle or a liposome. In some embodiments, a nanoparticle is a nanoparticle described in Chen et al., Mol Ther Methods Clin Dev. (2016) 3:16023, which is hereby incorporated by reference in its entirety. In some embodiments, a nanoparticle is a PLGA, polypeptide, poly(p-amino ester), DOPE, p-cyclodextrin-containing polycation, linear PEI, PAMAM dendrimer, branched PEI, chitosan or polyphosophoester nanoparticle. In some embodiments a LINC complex inhibitor is (covalently or non-covalently) associated with a cell-penetrating peptide (e.g. a protein transduction domain, trojan peptide, arginine-rich peptide, vectocell peptide), a cationic polymer, a cationic lipid or a viral carrier. In some embodiments a LINC complex inhibitor is associated with a peptide / polypeptide (e.g. antibody, peptide aptamer, ligand for a cell surface molecule / fragment thereof) or a nucleic acid (e.g. nucleic acid aptamer) capable of binding to a target cell of interest or an antigen thereof. In some embodiments, a LINC complex inhibitor is administered in the form of nucleic acid encoding the LINC complex inhibitor. For example, the LINC complex inhibitor may be administered in the form of nucleic acid encoding a peptide / polypeptide or nucleic acid LINC complex inhibitor, or an SSN system targeting a LINC complex protein. In some embodiments, a LINC complex inhibitor is administered in the form of nucleic acid encoding the factors required for production of a LINC complex inhibitor (e.g. nucleic acid encoding a precursor of the LINC complex inhibitor and / or nucleic acid encoding factors required for production / assembly of the LINC complex inhibitor). For example, the LINC complex inhibitor may be administered in the form of nucleic acid encoding factors required for production of a small molecule or biomolecular LINC complex inhibitor. The nucleic acid may be, or may be comprised in, a vector. A “vector” as used herein is a nucleic acid used as a vehicle to transfer exogenous nucleic acid into a cell. The vector may be a vector for expression of the nucleic acid in the target cell. Such vectors may include a promoter sequence 41 operably linked to the nucleic acid sequence to be expressed. A vector may also include a termination codon and expression enhancers. In this specification the term “operably linked” may include the situation where a selected nucleic acid sequence and regulatory nucleic acid sequence (e.g. promoter and / or enhancer) are covalently linked in such a way as to place the expression of the nucleotide sequence under the influence or control of the regulatory sequence (thereby forming an expression cassette). Thus a regulatory sequence is operably linked to the selected nucleic acid sequence if the regulatory sequence is capable of effecting transcription of the nucleic acid sequence. Where appropriate, the resulting transcript may then be translated into a desired polypeptide. Any suitable vectors, promoters, enhancers and termination codons known in the art may be used. Suitable vectors include viral vectors, e.g. retroviral vectors, lentiviral vectors, adenovirus vectors, adeno-associated virus vectors, vaccinia virus vectors and herpesvirus vectors, transposon-based vectors, and artificial chromosomes (e.g. yeast artificial chromosomes), e.g. as described in Maus et al., Annu Rev Immunol (2014) 32:189-225 or Morgan and Boyerinas, Biomedicines 2016 4, 9, which are both hereby incorporated by reference in its entirety. Byway of illustration, in Example 5 herein a dominant-negative version of SUN1 is administered using an adeno-associated viral vector. In some embodiments, a vector is selected based on tropism for a cell type / tissue / organ to which it is desired to deliver the nucleic acid, e.g. a cell type / tissue / organ affected by the disease to be treated / prevented in accordance with the invention (i.e. cells / tissue / an organ in which the symptoms of the disease manifest). For example, in some embodiments it is desired to deliver nucleic acid encoding a LINC complex inhibitor to muscle cells / tissue (e.g. cardiac and / or skeletal muscle cells / tissue), and vectors having a tropism for such cells / tissue may be employed in such embodiments. In some embodiments, a vector may be cardiotropic. In some embodiments, a vector may be myotropic. An AAV9 vector has recently been used to deliver Lmna-targeted CRISPR / Cas9-mediated gene therapy for HGPS in a Lmna-G609G mouse model (Santiago-Fernandez et al., Nat Med. (2019) 25(3):423-426 and Beyret et al., Nat Med. (2019) 25(3):419-422). In some embodiments, a vector may be an adeno-associated viral vector. In some embodiments, a vector may be an adeno-associated viral vector of one of the following serotypes: AAV9, AAV1, AAV6, AAV8, AAV2i8, AAV9.45, AAV10 or AAVrh.74. In some embodiments a vector comprises modification to increase binding to and / or transduction of a cell-type of interest (i.e. as compared to the level of binding / transduction by the unmodified vector). In some embodiments modification is to a capsid protein. In some embodiments a vector comprises a capsid protein comprising a cell-targeting peptide. In some embodiments the cell-targeting peptide is a cell-targeting peptide described in Biining and Srivastava, Molecular Therapy: Methods & Clinical Development (2019) 12: 248-265, which is hereby incorporated by reference in its entirety, e.g. a cell-targeting peptide shown in Table 1,2, 3 or 4. In some embodiments a vector comprises a capsid protein comprising mutation to one or more tyrosine residues, e.g. surface-exposed tyrosine residues. In some embodiments, the tyrosine residues are mutated to phenylalanine. In some embodiments a vector comprises a capsid protein in which tyrosine residues are mutated as described in Iida et al., Biomed Res Int. (2013) 2013: 974819, which is hereby incorporated by reference in its entirety. In some embodiments, a vector may be an adeno-associated viral vector described in Biining and Srivastava, supra. In some embodiments, a vector may be an adeno-associated viral vector described in Iida et al., supra. In some embodiments the nucleic acid / vector comprises one or more sequences for controlling expression of the nucleic acid. Accordingly, in some embodiments the nucleic acid / vector comprises a control element for inducible expression of the nucleic acid. A sequence for controlling expression of the nucleic acid may provide for expression of the nucleic acid by cells of a particular type or tissue. For example, expression may be under the control of a cell type- or tissue-specific promoter. By way of illustration, in Example 5 herein the expression of a construct encoding a dominant-negative version of SUN1 is under the control of a cardiomyocytespecific promoter. Promoters for cell type- or tissue-specific expression of a nucleic acid in accordance with the present invention can be selected in accordance with the disease to be treated / prevented. For example, the promoter may drive expression in cells / tissue / an organ affected by the disease (i.e. cells / tissue / an organ in which the symptoms of the disease manifest). In some embodiments a promoter may provide for expression in muscle cells / tissue (e.g. cardiac and / or skeletal muscle cells / tissue). In some embodiments, a promoter may be a cardiac or cardiomyocte-specific promoter (e.g. a cTNT, a-MHC or MLC2v promoter). In some embodiments, a promoter may be a skeletal muscle / striated muscle cell-specific promoter (e.g. a MCK, MHCK7 or desmin promoter). In some embodiments, a promoter may be a vascular endothelial cell-specific promoter (e.g. a Tie2 promoter). In some embodiments, a promoter may be a vascular smooth muscle cell-specific promoter (e.g. a SM22a promoter). In some embodiments, a promoter may be a monocyte / macrophage-specific promoter (e.g. a LysM promoter). 43 A sequence for controlling expression of the nucleic acid may provide for expression of the nucleic acid in response to e.g. an agent / signal. For example, expression may be under the control of inducible promoter. The agent may provide for inducible expression of the nucleic acid in vivo by administration of the agent to a subject having been administered with a modified cell according to the disclosure, or ex vivo / in vitro by administration of the agent to cells in culture ex vivo or in vitro. In some embodiments the nucleic acid(s) / vector(s) employ a conditional expression system for controlling expression of the nucleic acid encoding a LINC complex inhibitor by cells comprising the nucleic acid(s) / vector(s). “Conditional expression” may also be referred to herein as “inducible expression”, and refers to expression contingent on certain conditions, e.g. the presence of a particular agent. Conditional expression systems are well known in the art and are reviewed e.g. in Ryding et al. Journal of Endocrinology (2001) 171, 1-14, which is hereby incorporated by reference in its entirety. Multiple doses of the LINC complex inhibitor may be provided. One or more, or each, of the doses may be accompanied by simultaneous or sequential administration of another therapeutic agent. Multiple doses may be separated by a predetermined time interval, which may be selected to be one of 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days, or 1,2, 3, 4, 5, or 6 months. By way of example, doses may be given once every 7, 14, 21 or 28 days (plus or minus 3, 2, or 1 days). Treatment / prevention of diseases through LINC complex inhibition The present invention provides methods and articles (agents and compositions) for the treatment and / or prevention of diseases through LINC complex inhibition. Treatment / prevention of disease is achieved by LINC complex inhibition in e.g. a cell, tissue / organ / organ system / subject. Aspects of the present invention are concerned with the treatment / prevention of diseases in which LINC complex dysfunction is pathologically implicated. Such disease include e.g. nuclear envelopathies (e.g. laminopathies). The therapeutic utility of the agents and methods of the present invention extends to the treatment and / or prevention of any disease that would derive therapeutic / prophylactic benefit from LINC complex inhibition. The methods may be aimed at: delaying / preventing the onset of symptoms of the disease; reducing the severity of (i.e. alleviating) the symptoms of the disease; reversing the symptoms of the disease; reducing morbidity of subjects having the disease; reducing mortality of subjects having the disease; and / or delaying / preventing progression the disease (e.g. to a later stage). Aspects of the invention concern the treatment of diseases associated with mutation to a given gene or plurality of genes. Herein, diseases which are “associated with” mutations to a given gene / genes are diseases which are caused or exacerbated by such mutations, or for which such mutations are a risk factor for the development or progression of the disease. In some embodiments, the mutation gives rise to one or more of the following in cells comprising one or more copies of the mutant allele of the gene as compared to cells comprising two copies of (i.e. homozygous for) the non-mutated (wildtype) reference allele of the gene: a reduced level of a gene product (e.g. RNA and / or protein (or particular isoform thereof)) of the wildtype allele; an increased level of a gene product of a nonwildtype allele; an increased level of a gene product of the wildtype allele. Aspects of the present invention concern the treatment / prevention of nuclear envelopathies. Nuclear envelopathies are diseases / pathological conditions associated with mutations to genes encoding nuclear envelope proteins (i.e. proteins contained in, or directly / indirectly associated with, the ONM, perinuclear space or INM). Nuclear envelopathies are reviewed e.g. by Chi et al., Journal of Biomedical Science (2009) 16:96, which is hereby incorporated by reference in its entirety. Nuclear envelopathies include diseases / pathological conditions associated with mutations in LMNA, LMNB1, LMNB2, EMD, LAP2, LBR, ZMPSTE24, SYNE-1 and NUP62. In particular, aspects of the present invention are concerned with the treatment / prevention of laminopathies. Laminopathies are reviewed e.g. by Burke and Stewart, Nat Rev Mol Cell Biol. (2013) 14(1):13-24, and Hah and Kim, Cells (2019) 8(3): 231, which are both hereby incorporated by reference in their entirety. Laminopathies are commonly associated with tissue-specific defects in load bearing at the nuclear level, which can reduce the tolerance of cells to physical forces. In the experimental examples herein, the inventors demonstrate that LINC complex inhibition ameliorates the symptoms of a range of laminopathies. As used herein, a “laminopathy” is a disease / pathological condition associated with mutation to a gene encoding a lamin. Genes encoding lamins include LMNA (which encodes lamins A and C), and LMNB1, LMNB2, which encode lamins B1 and B2. Accordingly, aspects of the present invention concern the treatment / prevention of diseases associated with mutation to LMNA, LMNB1 and / or LMNB2. In some embodiments the mutation is known or predicted to reduce the level of a lamin isoform encoded by the wildtype allele of a gene enoding a lamin (e.g. LMNA, LMNB1 or LMNB2). In some embodiments the mutation is a missense mutation. In some embodiments the mutation is known or predicted to result in the production of a truncated version of a lamin encoded by the wildtype allele of a gene enoding a lamin. In some embodiments the mutation is known or predicted to result in the production of a lamin which is misfolded and / or degraded. In some embodiments the mutation is known or predicted to increase the level of a lamin isoform encoded by the wildtype allele of a gene enoding a lamin (e.g. LMNA, LMNB1 or LMNB2). In some embodiments the mutation is known or predicted to increase the level of a disease-associated lamin variant (e.g. progerin). In some embodiments the mutation is known or predicted to increase the level of a lamin encoded by a disease-associated allele of a gene enoding a lamin. In some embodiments the laminopathy is a skeletal muscle laminopathy. In some embodiments the laminopathy is a myopathy. In some embodiments the laminopathy is a LMNA mutation-associated myopathy. In some embodiments, the disease to be treated / prevented in accordance with the present invention is characterised by one or more of myopathy, cardiomyopathy, dilated cardiomyopathy, muscular dystrophy, cardiac muscular dystrophy, skeletal muscular dystrophy, progeria, neuropathy, lipoatrophy, skeletal dysplasia, lipodystrophy, leukodystrophy ordermopathy. In some embodiments, the disease to be treated / prevented in accordance with the present invention is characterised by one or more of muscular dystrophy, cardiac muscular dystrophy or skeletal muscular dystrophy. In some embodiments the laminopathy is associated with mutation to LMNA, LMNB1 or LMNB2. In some embodiments the laminopathy is selected from Hutchinson-Gilford Progeria Syndrome; Emery-Dreifuss Muscular Dystrophy; Emery-Dreifuss Muscular Dystrophy 2, Autosomal Dominant; Lipodystrophy, Partial, Acquired; Epilepsy, Progressive Myoclonic, 9; Charcot-Marie-Tooth Disease, Axonal, Type 2e; Muscular Dystrophy; Lipodystrophy, Familial Partial, Type 2; Cardiomyopathy, Dilated, 1h; Pelger-Huet Anomaly; Reynolds Syndrome; Muscular Disease; Leukodystrophy; Dilated Cardiomyopathy; Muscular Dystrophy, Congenital, Lmna-Related; Mandibuloacral Dysplasia with Type a Lipodystrophy; Cardiomyopathy, Dilated, 1a; Restrictive Dermopathy, Lethal; Familial Partial Lipodystrophy; Epilepsy; Lipoatrophy with Diabetes, Leukomelanodermic Papules, Liver Steatosis, and Hypertrophic Cardiomyopathy; Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant; Acquired Generalized Lipodystrophy; Emery-Dreifuss Muscular Dystrophy 3, Autosomal Recessive; Charcot-Marie-Tooth Disease; Charcot-Marie-Tooth Disease, Axonal, Type 2b1; Cardiomyopathy, Dilated, 1b; Atrial Standstill 1; Limb-Girdle Muscular Dystrophy; Cardiomyopathy, Dilated, with Hypergonadotropic Hypogonadism; Heart-Hand Syndrome, Slovenian Type; Monogenic Diabetes; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiomyopathy, Dilated, 1e; Aging; Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy Syndrome; Adrenomyodystrophy; Atypical Werner Syndrome; Endometriosis; Spinocerebellar Ataxia 31; 46 Progressive Muscular Atrophy; Neurogenic Bowel; Autosomal Dominant Leukodystrophy with Autonomic Disease; Werner Syndrome; Myopathy; Lmna-Related Dilated Cardiomyopathy; Muscular Dystrophy, Congenital, 1b; Hypertrophic Cardiomyopathy; Left Ventricular Noncompaction; Diabetes Mellitus, Noninsulin-Dependent; Arrhythmogenic Right Ventricular Dysplasia, Familial, 9; Heart Disease; Atrial Fibrillation; Cardiac Conduction Defect; Myoclonus; Progressive Myoclonus Epilepsy; Myoclonus Epilepsy; Peripheral Nervous System Disease; Tooth Disease; Atrioventricular Block; Myofibrillar Myopathy; Autosomal Dominant Limb-Girdle Muscular Dystrophy; Lmna-Related Cardiocutaneous Progeria Syndrome; Amyotrophic Lateral Sclerosis 1; Neural Tube Defects; Cervical Cancer; Neural Tube Defects, Folate-Sensitive; Cerebral Degeneration; Acanthosis Nigricans; 3-Hydroxyacyl-Coa Dehydrogenase Deficiency; Congenital Fiber-Type Disproportion; Acroosteolysis; Wolff-Parkinson-White Syndrome; Sick Sinus Syndrome; Calcinosis; Undifferentiated Pleomorphic Sarcoma; Ventricular Tachycardia, Catecholaminergic Polymorphic, 1, with or without Atrial Dysfunction and / or Dilated Cardiomyopathy; Lipodystrophy, Familial Partial, Type 1; Axonal Neuropathy; Paroxysmal Ventricular Fibrillation; Brugada Syndrome 5; Rigid Spine Muscular Dystrophy; Limb-Girdle Muscular Dystrophy Type 1 b; Insulin-Resistant Acanthosis Nigricans, Type a; Generalized Lipodystrophy-Associated Progeroid Syndrome; Osteoporosis; Rigid Spine Muscular Dystrophy 1; Neuropathy; Catecholaminergic Polymorphic Ventricular Tachycardia; Cataract; Bethlem Myopathy 1; Congenital Generalized Lipodystrophy; Restrictive Cardiomyopathy; Muscular Dystrophy, Congenital Merosin-Deficient, 1a; Proximal Spinal Muscular Atrophy; Muscular Dystrophy-Dystroglycanopathy , Type B, 5; Lipodystrophy, Congenital Generalized, Type 1; Emery-Dreifuss Muscular Dystrophy 1, X-Linked; Cardiomyopathy, Dilated, 1d; Myopathy, Proximal, and Ophthalmoplegia; Muscle Tissue Disease; Ovarian Cystadenoma; Emerinopathy; Fanconi Anemia, Complementation Group a; Body Mass Index Quantitative Trait Locus 11; Myelodysplastic Syndrome; Skin Disease; Anorexia Nervosa; Spinal Muscular Atrophy; Inclusion Body Myositis; Aniridia 1; Myositis; Trichohepatoenteric Syndrome 1; Neuromuscular Disease; Nutritional Deficiency Disease; Thoracic Outlet Syndrome; Muscle Disorders; Muscular Atrophy; Hallermann-Streiff Syndrome; RereRelated Disorders; Miller-Dieker Lissencephaly Syndrome; Lipodystrophy, Congenital Generalized, Type 4; Lipodystrophy, Familial Partial, Type 3; Wiedemann-Rautenstrauch Syndrome; Lipodystrophy, Congenital Generalized, Type 2; Ataxia Neuropathy Spectrum; Alopecia, Neurologic Defects, and Endocrinopathy Syndrome; Lipodystrophy, Familial Partial, Type 4; Second-Degree Atrioventricular Block; Acute Necrotizing Encephalopathy; Median Neuropathy; Intrinsic Cardiomyopathy; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Right Dominant Form; Prolapse of Female Genital Organ; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Biventricular Form; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Left Dominant Form; Complete Generalized Lipodystrophy; Blood Group--Ahonen; Autosomal Semi-Dominant Severe Lipodystrophic Laminopathy; Ulnar Nerve Lesion; Pelvic Muscle Wasting; Alzheimer Disease; Stroke, Ischemic; Ataxia-Telangiectasia; Spondyloarthropathy 1; Human Immunodeficiency Virus Type 1; Neuroblastoma; Vascular Disease; Nervous System Disease; Respiratory Failure; Turner Syndrome; Carpal Tunnel Syndrome; Barrett Esophagus; Sleep Apnea; Cerebrovascular Disease; Proteasome-Associated Autoinflammatory Syndrome 1; Joubert Syndrome 1; Viral Infectious Disease; Dementia; Personality Disorder; Neuropathy, Hereditary Sensory and Autonomic, Type Hi; Lowe Oculocerebrorenal Syndrome; Diabetes Mellitus; Fatty Liver Disease; Leigh Syndrome; Muscular Dystrophy, Duchenne Type; Hydrocephalus; Dermatomyositis; Hirschsprung Disease 1; Long Qt Syndrome; Angelman Syndrome; Central Nervous System Disease; Congenital Disorder of Glycosylation, Type in; Alacrima, Achalasia, and Mental Retardation Syndrome; Polycystic Ovary Syndrome; Hypoglycemia; Muscle Hypertrophy; Kearns-Sayre Syndrome; Cone-Rod Dystrophy 2; Aicardi-Goutieres Syndrome; Andersen Cardiodysrhythmic Periodic Paralysis; Muscular Dystrophy, Becker Type; Legg-Calve-Perthes Disease; Androgen Insensitivity Syndrome; Ehlers-Danlos Syndrome; Axenfeld-Rieger Syndrome; Muscular Dystrophy-Dystroglycanopathy , Type C, 5; Glomerulonephritis; Seizure Disorder; Chikungunya; West Syndrome; Ullrich Congenital Muscular Dystrophy 1; Focal Segmental Glomerulosclerosis; Walker-Warburg Syndrome; Renal Hypodysplasia / aplasia 1; Popliteal Pterygium Syndrome; Microcephaly; Childhood Type Dermatomyositis; Distal Arthrogryposis; Myocarditis; Arterial Tortuosity Syndrome; Scoliosis; Membranous Nephropathy; Microvascular Complications of Diabetes 3; Epidermolysis Bullosa; Short Syndrome; Hyperekplexia; Nonalcoholic Fatty Liver Disease; Muscular Dystrophy-Dystroglycanopathy , Type a, 4; Congenital Hydrocephalus; Ataxia, Combined Cerebellar and Peripheral, with Hearing Loss and Diabetes Mellitus; Cardiac Arrhythmia; Muscular Dystrophy-Dystroglycanopathy , Type a, 1; Ptosis; Laryngitis; Ablepharon-Macrostomia Syndrome; Supravalvular Aortic Stenosis; Myopathy, Congenital; Metabolic Encephalomyopathic Crises, Recurrent, with Rhabdomyolysis, Cardiac Arrhythmias, and Neurodegeneration; Lissencephaly 1; Polycystic Liver Disease 1 with or without Kidney Cysts; Idiopathic Inflammatory Myopathy; Epidermolysis Bullosa Simplex; Focal Segmental Glomerulosclerosis 1; Gonadal Dysgenesis; Gyrate Atrophy of Choroid and Retina; Syringomyelia; Ichthyosis Vulgaris; Arthrogryposis, Distal, Type 1a; Acute Insulin Response; Brachydactyly; Cerebellar Hypoplasia; Craniometaphyseal Dysplasia, Autosomal Dominant; Alport Syndrome 1, X-Linked; Lissencephaly; Muscular Dystrophy-Dystroglycanopathy , Type B, 6; Diarrhea 5, with Tufting Enteropathy, Congenital; Junctional Epidermolysis Bullosa; Aicardi-Goutieres Syndrome 1; Miyoshi Muscular Dystrophy; Retinitis; Marden-Walker Syndrome; Neuroretinitis; Polyglucosan Body Myopathy 1 with or without Immunodeficiency; Epidermolysis Bullosa, Junctional, HerlitzType; Macroglossia; Parkinson Disease 15, Autosomal Recessive Early-Onset; Myopathy, Myofibrillar, 3; Microvascular Complications of Diabetes 7; Muscle Eye Brain Disease; Melkersson-Rosenthal Syndrome; Myopathy, X-Linked, with Excessive Autophagy; Choroiditis; Muscular Dystrophy, LimbGirdle, Autosomal Recessive 8; Crouzon Syndrome with Acanthosis Nigricans; Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 6; Polymicrogyria; Dystrophinopathies; Microvascular Complications of Diabetes 6; Microvascular Complications of Diabetes 4; Hypotonia; Pontocerebellar Hypoplasia; Congenital Fibrosarcoma; Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies; Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 7; Myopathy, Congenital, with Fiber-Type Disproportion; Amelogenesis Imperfecta, Type Ig; Refractory Anemia; Fibrosis of Extraocular Muscles, Congenital, 1; Ataxia and Polyneuropathy, Adult-Onset; Al-Raqad Syndrome; Senile Cataract; Muscular Dystrophy-Dystroglycanopathy , Type C, 1; Neuronal Migration Disorders; Ayme-Gripp Syndrome; Primary Agammaglobulinemia; Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2a; Cerebritis; Muscular Dystrophy, Congenital, Megaconial Type; Autosomal Recessive Limb-Girdle Muscular Dystrophy; Alkuraya-Kucinskas Syndrome; Muscular Dystrophy-Dystroglycanopathy , Type C, 4; Congenital Muscular Dystrophy Type 1a; Behr Syndrome; Dandy-Walker Complex; Muscular Dystrophy-Dystroglycanopathy , Type C, 2; Emery-Dreifuss Muscular Dystrophy, X-Linked; Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 3; Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2d; Brain Small Vessel Disease 1 with or without Ocular Anomalies; Familial Isolated Dilated Cardiomyopathy; Epithelial Recurrent Erosion Dystrophy; Muscular Dystrophy-Dystroglycanopathy; Mycobacterium Avium Complex Infections; Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2I; Visual Epilepsy; Aneurysm of Sinus of Valsalva; Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2b; Creatine Phosphokinase, Elevated Serum; Spastic Paraplegia, Ataxia, and Mental Retardation; Multinucleated Neurons, Anhydramnios, Renal Dysplasia, Cerebellar Hypoplasia, and Hydranencephaly; Patulous Eustachian Tube; Autosomal Genetic Disease; Ck Syndrome; Neuronitis; Hyperekplexia 1; Reducing Body Myopathy; Polymicrogyria, Bilateral Temporooccipital; Isolated Hyperckemia; Charcot-Marie-Tooth Disease, Axonal, Type 2b2; Cardioneuromyopathy with Hyaline Masses and Nemaline Rods; Congenital Muscular Dystrophy without Intellectual Disability; Blood Group, I System; Salih Myopathy; Adducted Thumbs Syndrome; Dural Sinus Malformation; Blood Group, Dombrock System; Blood Group, Colton System; Arthrochalasia Ehlers-Danlos Syndrome; Lama2-Related Muscular Dystrophy; Muscular Dystrophy, Congenital, with Infantile Cataract and Hypogonadism; Intrauterine Infections; Muscular Dystrophy, Congenital, Merosin-Positive; Congenital Muscular Dystrophy with Cerebellar Involvement; Fukuyama Type Muscular Dystrophy; Chronic Lymphoproliferative Disorder of Natural Killer Cells; Congenital Muscular Dystrophy with Intellectual Disability; Amelogenesis Imperfecta Hypoplastic Type, Ig; Androgen Insensitivity Syndrome, Mild; Muscular Dystrophy, Congenital, Producing Arthrogryposis; Congenital Muscular Alpha-Dystroglycanopathy with Brain and Eye Anomalies; Collagen Vi-Related Myopathy; Emery-Dreifuss Muscular Dystrophy, Dominant Type; Congenital Muscular Dystrophy Due to Dystroglycanopathy; Proximal Myopathy with Focal Depletion of Mitochondria; Infantile Scoliosis. In some embodiments the laminopathy is a laminopathy associated with mutation to LMNA. In some embodiments the laminopathy is selected from Hutchinson-Gilford Progeria Syndrome; Dilated Cardiomyopathy; Muscular Dystrophy, Congenital, Lmna-Related; Emery-Dreifuss Muscular Dystrophy 2, Autosomal Dominant; Muscular Dystrophy; Mandibuloacral Dysplasia with Type a Lipodystrophy; Cardiomyopathy, Dilated, 1a; Charcot-Marie-Tooth Disease; Limb-Girdle Muscular Dystrophy; Cardiomyopathy, Dilated, with Hypergonadotropic Hypogonadism; Emery-Dreifuss Muscular Dystrophy 3, Autosomal Recessive; Lipodystrophy, Familial Partial, Type 2; Emery-Dreifuss Muscular Dystrophy; Charcot-Marie-Tooth Disease, Axonal, Type 2b1; Heart-Hand Syndrome, Slovenian Type; Aging; Familial Partial Lipodystrophy; Restrictive Dermopathy, Lethal; Arrhythmogenic Right Ventricular Cardiomyopathy; Tooth Disease; Heart Disease; Werner Syndrome; Hypertrophic Cardiomyopathy; Left Ventricular Noncompaction; Atrioventricular Block; Calcinosis; Acroosteolysis; Autosomal Dominant Limb-Girdle Muscular Dystrophy; Diabetes Mellitus, Noninsulin- 49 Dependent; Osteoporosis; Atrial Fibrillation; Atrial Standstill 1; Acanthosis Nigricans; Cardiac Conduction Defect; Catecholaminergic Polymorphic Ventricular Tachycardia; Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy Syndrome; Sick Sinus Syndrome; Pelger-Huet Anomaly; Charcot-Marie-Tooth Disease, Axonal, Type 2e; Congenital Generalized Lipodystrophy; Restrictive Cardiomyopathy; Congenital Fiber-Type Disproportion; Lipodystrophy, Congenital Generalized, Type 1; Myofibrillar Myopathy; Lipodystrophy, Familial Partial, Type 1; Axonal Neuropathy; Atypical Werner Syndrome; Ovarian Cystadenoma; Fanconi Anemia, Complementation Group a; Body Mass Index Quantitative Trait Locus 11; Skin Disease; Rigid Spine Muscular Dystrophy 1; Neuromuscular Disease; Hallermann-Streiff Syndrome; Bethlem Myopathy 1; Acquired Generalized Lipodystrophy; Cardiomyopathy, Dilated, 1e; Lipodystrophy, Congenital Generalized, Type 4; Undifferentiated Pleomorphic Sarcoma; Lipodystrophy, Familial Partial, Type 3; Muscular Dystrophy, Congenital Merosin-Deficient, 1a; Proximal Spinal Muscular Atrophy; Muscular Dystrophy-Dystroglycanopathy , Type B, 5; Muscular Dystrophy, Congenital, 1b; Reynolds Syndrome; Wiedemann-Rautenstrauch Syndrome; Emery-Dreifuss Muscular Dystrophy 1, X-Linked; Lipodystrophy, Congenital Generalized, Type 2; Monogenic Diabetes; Cardiomyopathy, Dilated, 1d; Myopathy, Proximal, and Ophthalmoplegia; Muscle Tissue Disease; Lipodystrophy, Familial Partial, Type 4; Cardiomyopathy, Dilated, 1h; Second-Degree Atrioventricular Block; Median Neuropathy; Intrinsic Cardiomyopathy; Prolapse of Female Genital Organ; Complete Generalized Lipodystrophy; Rigid Spine Muscular Dystrophy; Emerinopathy; Ulnar Nerve Lesion; Limb-Girdle Muscular Dystrophy Type 1b; Lmna-Related Dilated Cardiomyopathy; Pelvic Muscle Wasting; Generalized Lipodystrophy-Associated Progeroid Syndrome; Muscular Disease; Cardiomyopathy, Dilated, 1b; Autosomal Genetic Disease; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Right Dominant Form; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Biventricular Form; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Left Dominant Form; Lmna-Related Cardiocutaneous Progeria Syndrome; Autosomal Semi-Dominant Severe Lipodystrophic Laminopathy. In some embodiments the disease to the treated / prevented in accordance with the present invention is selected from a disease associated with a cDNA or protein variant indicated in Table 1. In some embodiments the disease to the treated / prevented in accordance with the present invention is selected from a disease indicated in Table 1. In some embodiments the disease to the treated / prevented in accordance with the present invention is selected from a disease indicated in normal font in Table 1. In some embodiments the disease to the treated / prevented in accordance with the present invention is selected from a disease indicated in bold font in Table 1. Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Om^ SymS _ 17811 c.1771T>A Substitution p.Cys591Ser Substitution Tail - Acrogeria, Gottron Type 201200 :02: % 18255 c.418_438dupCTGCTGAAC TCCAAGGAGGCC Duplication p.Leul 40_Ala146dup Duplication 1B - Arrhythmogenic cardiomyopathy - । । 1 / 010 1 17439 c.1039G>A Substitution p.Glu347Lys Substitution 2B ARVD7 Arrhythmogenic right ventricular cardiomyopathy (ARVD7) 609160 □0 18492 C.1930OT Substitution p.Arg644Cys Substitution Tail ARVD7 Arrhythmogenic right ventricular cardiomyopathy 609160 % 9157 C. 171 SOT Substitution p.Ser573Leu Substitution Tail - Arthropathy syndrome, autosomal recessive - - 18299 c.1494G>A Substitution p.Trp498X Substitution Tail AF Atrial fibrillation - - 18301 C.175OG Substitution p.Leu59Val Substitution 1A APS Atypical progeroid syndrome - - 8885 c.169G>C Substitution p.Ala57Pro Substitution 1A WRN Atypical Werner syndrome 277700 # 8886 C.398G>T Substitution p.Arg133Leu Substitution 1B WRN Atypical Werner syndrome 277700 # 11462 c.398G>T Substitution p.Arg133Leu Substitution 1B WRN Atypical Werner syndrome 277700 # 9232 C.398G>T Substitution p.Arg133Leu Substitution 1B WRN Atypical Werner syndrome 277700 # 11509 c.398G>T Substitution p.Arg133Leu Substitution 1B WRN Atypical Werner syndrome 277700 # 11670 c.398G>T Substitution p.Arg133Leu Substitution 1B WRN Atypical Werner syndrome 277700 # 8888 c.419T>G Substitution p.Leul 40Arg Substitution 1B WRN Atypical Werner syndrome 277700 # 13457 c.506delT Deletion p.Val169GlyfsX7 Frame shift 1B WRN Atypical Werner syndrome 277700 # 13350 c.898G>A Substitution p.Asp300Asn Substitution 2B WRN Atypical Werner syndrome 277700 # 17875 c.898G>A Substitution p.Asp300Asn Substitution 2B WRN Atypical Werner syndrome 277700 # 11767 c.1130G>T Substitution p.Arg377Leu Substitution 2B AD-SMA Autosomal dominant spinal muscular dystrophy 182980 # 11766 c.1477C>T Substitution p.Gln493X Substitution Tail AD-SMA Autosomal dominant spinal muscular dystrophy 182980 # 9205 c.? Unknown p.Glu33Asp Substitution 1A - Axonal neuropathy, muscular dystrophy, cardiac disease - 8994 c.99G>T Substitution p.Glu33Asp Substitution 1A - Axonal neuropathy, muscular dystrophy, cardiac disease, leuconychia - 1                                                              1 r / SG20 1 12416 C.1621OT Substitution p.Arg541 Cys Substitution Tail - Cardiac arrhythmia - - © 12399 C.673OT Substitution p.Arg225X Substitution L12 CCD Cardiac conduction defect 115080 17808 c.695G>T Substitution p.Gly232Val Substitution L12 CCD Cardiac conduction defect 115080 #= 13449 c.799T>C Substitution p.Tyr267His Substitution 2B CCD Cardiac conduction defect 115080 # Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Orrjr syng . 14260 C.178OG Substitution p.Arg60Gly Substitution 1A - Cardiomyopathy with advanced AV block and arrhythmia - 14256 C.184OG Substitution p.Arg62Gly Substitution 1A - Cardiomyopathy with advanced AV block and arrhythmia - 010 / 1 I 14018 c.497G>C Substitution p.Arg166Pro Substitution 1B - Cardiomyopathy with advanced AV block and arrhythmia - go '00 14258 c.575A>T Substitution p.Asp192Val Substitution 1B - Cardiomyopathy with advanced AV block and arrhythmia - - 14007 C.673OT Substitution p.Arg225X Substitution L12 - Cardiomyopathy with advanced AV block and arrhythmia - - 14015 c.775T>C Substitution p.Tyr259His Substitution L2 - Cardiomyopathy with advanced AV block and arrhythmia - - 14016 c.775T>C Substitution p.Tyr259His Substitution L2 - Cardiomyopathy with advanced AV block and arrhythmia - - 14011 c.815_818delACAAinsCCA GAC Indel p.Asp272AlafsX208 Frame shift 2B - Cardiomyopathy with advanced AV block and arrhythmia - - 14012 c.815_818delACAAinsCCA GAC Indel p.Asp272AlafsX208 Frame shift 2B - Cardiomyopathy with advanced AV block and arrhythmia - - 11652 C.- 3_12delGCCATGGAGACCC CG Deletion p.Met1_Pro4del Deletion Head CMT2 Charcot-Marie-Tooth disease type 2 118210 # 13374 c.1496_1496delC Deletion p.Ala499ValfsX141 Frame shift Tail CMT2 Charcot-Marie-Tooth disease type 2 118210 # 17199 c.1910T>C Substitution p.Phe637Ser Substitution Tail CMT2 Charcot-Marie-Tooth disease type 2 118210 # 8840 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 11415 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 11416 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 8997 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 11840 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 11839 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 11838 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 11837 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 id 12087 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 13414 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 13415 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 13416 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syn^ . 13417 c.892C>T Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 id 13418 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 i i 202 13419 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 I I 1 / 0 n 13420 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 108 0 13421 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 13422 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13423 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13424 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13425 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13426 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13427 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13428 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13429 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13430 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13431 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13432 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13433 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13434 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13435 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13436 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 13437 C.892OT Substitution p.Arg298Cys Substitution 2B CMT2B1 Charcot-Marie-Tooth disease type 2B1 605588 # 17886 c.80C>T Substitution p.Thr27lle Substitution Head CFTDM Congenital fiber type disproportion 255310 # 18472 c.907T>C Substitution p.Ser303Pro Substitution 2B CFTDM Congenital fiber type disproportion 255310 # 18473 c.907T>C Substitution p.Ser303Pro Substitution 2B CFTDM Congenital fiber type disproportion 255310 # 18474 c.907T>C Substitution p.Ser303Pro Substitution 2B CFTDM Congenital fiber type disproportion 255310 tn 18475 c.907T>C Substitution p.Ser303Pro Substitution 2B CFTDM Congenital fiber type disproportion 255310 i<z> 18144 c.91G>A Substitution p.Glu31Lys Substitution Head CMD Congenital muscular dystrophy - 0 18148 c.91_93delGAG Deletion p.Glu31X Substitution Head CMD Congenital muscular dystrophy - ■© 17813 c.93G>C Substitution p.Glu31Asp Substitution Head CMD Congenital muscular dystrophy - © Ul 18146 c.94_96delAAG Deletion p.Lys32X Substitution 1A CMD Congenital muscular dystrophy - 4— © Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sym^ 16402 c.104T>C Substitution p.Leu35Pro Substitution 1A CMD Congenital muscular dystrophy - .0 16287 c.115A>T Substitution p.Asn39Tyr Substitution 1A CMD Congenital muscular dystrophy - © "KJ 18150 c.117T>G Substitution p.Asn39Lys Substitution 1A CMD Congenital muscular dystrophy - -© 18153 c.143G>C Substitution p.Arg48Pro Substitution 1A CMD Congenital muscular dystrophy - © “00 18156 c.422T>C Substitution p.Leu141Pro Substitution 1B CMD Congenital muscular dystrophy - .00 13462 c.745C>T Substitution p.Arg249Trp Substitution 2A CMD Congenital muscular dystrophy - - 16404 C.745OT Substitution p.Arg249Trp Substitution 2A CMD Congenital muscular dystrophy - - 17758 C.745OT Substitution p.Arg249Trp Substitution 2A CMD Congenital muscular dystrophy - - 18158 c.745C>T Substitution p.Arg249Trp Substitution 2A CMD Congenital muscular dystrophy - - 11816 c.1072G>A Substitution p.Glu358Lys Substitution 2B CMD Congenital muscular dystrophy - - 18161 c.1117A>G Substitution p.lle373Val Substitution 2B CMD Congenital muscular dystrophy - - 18166 c.1118T>A Substitution p.lle373Asn Substitution 2B CMD Congenital muscular dystrophy - - 13460 c.1139T>C Substitution p.Leu380Ser Substitution 2B CMD Congenital muscular dystrophy - - 18169 c.1147G>A Substitution p.Glu383Lys Substitution 2B CMD Congenital muscular dystrophy - - 18171 C.1147G>A Substitution p.Glu383Lys Substitution 2B CMD Congenital muscular dystrophy - - 18163 c.1151A>G Substitution p.Glu384Gly Substitution 2B CMD Congenital muscular dystrophy - - 11817 C.1162OT Substitution p.Arg388Cys Substitution Tail CMD Congenital muscular dystrophy - - 17473 c.1330 1338dupGAGGTGG AT Duplication p.Glu444_Asp446dup Duplication Tail CMD Congenital muscular dystrophy - - 11818 c.1368_1370delCAA Deletion p.Asn456del Deletion Tail CMD Congenital muscular dystrophy - - 18238 c.1489-14_1489-7delTTTCTCCT Deletion P? Unknown Unknown CMD Congenital muscular dystrophy - - 16951 c.1445G>A Substitution p.Arg482Gln Substitution Tail T2D DIABETES MELLITUS, NONINSULINDEPENDENT; NIDDM 125853 # 13171 c.? Unknown p.Lys260Asn Substitution L2 CMD1A Dilated cardiomyopathy 1A 115200 # 8832 c.16C>T Substitution p.Gln6X Substitution Head CMD1A Dilated cardiomyopathy 1A 115200 9397 c.28_29insA Insertion p.Thr10AsnfsX31 Frame shift Head CMD1A Dilated cardiomyopathy 1A 115200 I—I T / S % 11627 c.31delC Deletion p.Arg11AlafsX85 Frame shift Head CMD1A Dilated cardiomyopathy 1A 115200 14254 c.73C>G Substitution p.Arg25Gly Substitution Head CMD1A Dilated cardiomyopathy 1A 115200 102( ft 13155 c.82C>T Substitution p.Arg28Trp Substitution Head CMD1A Dilated cardiomyopathy 1A 115200 #= 13563 C.155T>C Substitution p.Leu52Pro Substitution 1A CMD1A Dilated cardiomyopathy 1A 115200 1—1 504( Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sym^ 13379 c.176T>G Substitution p.Leu59Arg Substitution 1A CMD1A Dilated cardiomyopathy 1A 115200 #° 13378 c.176T>G Substitution p.Leu59Arg Substitution 1A CMD1A Dilated cardiomyopathy 1A 115200 #S 8748 c.178C>G Substitution p.Arg60Gly Substitution 1A CMD1A Dilated cardiomyopathy 1A 115200 13192 c.203_208delAGGTGG Deletion p.Glu68_Val69del Deletion 1A CMD1A Dilated cardiomyopathy 1A 115200 % >80 17742 c.232G>A Substitution p.Lys78Glu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 #00 9163 c.244G>A Substitution p.Glu82Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16139 c.244G>A Substitution p.Glu82Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 8749 c.254T>G Substitution p.Leu85Arg Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 8865 c.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11618 C.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13080 c.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13157 c.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 14030 c.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16966 c.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17777 C.266G>T Substitution p.Arg89Leu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13613 C.274OT Substitution p.Leu92Phe Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 8844 c.289A>G Substitution p.Lys97Glu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11620 c.289A>G Substitution p.Lys97Glu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13159 c.289A>G Substitution p.Lys97Glu Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13082 C.302G>C Substitution p.Arg101Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16954 c.302G>C Substitution p.Arg101Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 8843 c.331G>T Substitution p.GluWX Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11619 c.331G>T Substitution p.GluWX Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13199 c.331G>T Substitution p.GluWX Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 16935 c.348_349insG Insertion p.Lys117GlufsX10 Frame shift 1B CMD1A Dilated cardiomyopathy 1A 115200 #n H - 13089 c.357-1 G>T Substitution P? Unknown Unknown CMD1A Dilated cardiomyopathy 1A 115200 9148 c.394G>C Substitution p.Ala132Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 17029 c.394G>C Substitution p.Ala132Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 #O 17028 c.394G>C Substitution p.Ala132Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 9297 c.425_426insGGCACTGGA GGCTCTGCTGAA Insertion p.Leu141_Asn142insLys AspLeuAspAlaLeuLeu Insertion 1B CMD1A Dilated cardiomyopathy 1A 115200 ►407 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Svml^ 9010 C.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # u 11473 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # s 11474 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 2 11475 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 % >80 11476 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 #00 11477 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 9150 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16162 C.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16163 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16164 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16165 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17038 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17037 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17036 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17024 C.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17022 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17021 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17020 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17019 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17018 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17023 c.427T>C Substitution p.Ser143Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17661 c.448A>T Substitution p.Thr150Ser Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 8879 c.481G>A Substitution p.Glu161 Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13161 c.481G>A Substitution p. Glut 61 Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13162 c.481G>A Substitution p.Glu161 Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # Q 13163 C.481G>A Substitution p.Glu161 Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 % S / J 13328 c.481G>A Substitution p.Glu161 Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 a * 13617 c.481G>A Substitution p.Glu161 Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # * © 13091 c.497G>C Substitution p.Arg166Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 % SO / 16968 c.497G>C Substitution p.Arg166Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 040 it Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syn^ 16969 C.497G>C Substitution p.Arg166Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 13165 c.548T>C Substitution p.Leu183Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 J02 0 18267 c.563T>G Substitution p.Leu188Arg Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 0 / 1 1 16160 C.565OT Substitution p.Arg189Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 108 0 8845 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 9011 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11507 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 9149 c.568C>T Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11621 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11782 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 11790 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13167 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16167 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17034 c.568C>T Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17033 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17032 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 17031 C.568OT Substitution p.Arg190Trp Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13093 c.569G>A Substitution p.Arg190Gln Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 13330 c.569G>A Substitution p.Arg190Gln Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 16976 c.569G>A Substitution p.Arg190Gln Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 9165 c.575A>G Substitution p.Asp192Gly Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 14200 c.575A>G Substitution p.Asp192Gly Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 8750 C.585OG Substitution p.Asn195Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 # 12393 C.585OA Substitution p.Asn195Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 % 11668 c.607G>A Substitution p.Glu203Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 '2 16978 c.607G>A Substitution p.Glu203Lys Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 8751 c.608A>G Substitution p.Glu203Gly Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 13332 c.608A>T Substitution p.Glu203Val Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 13095 c.629T>G Substitution p.lle210Ser Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 16971 c.629T>G Substitution p.lle210Ser Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syr^ I 8901 c.640-10A>G Substitution P? Unknown Unknown CMD1A Dilated cardiomyopathy 1A 115200 ;O 8864 c.644T>C Substitution p.Leu215Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 202 □ 16980 c.644T>C Substitution p.Leu215Pro Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 □ 0 / 1 I 13169 c.656A>C Substitution p.Lys219Thr Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 □ 801 LJ 13335 c.656A>C Substitution p.Lys219Thr Substitution 1B CMD1A Dilated cardiomyopathy 1A 115200 11669 c.673C>T Substitution p.Arg225X Substitution L12 CMD1A Dilated cardiomyopathy 1A 115200 # 17607 c.673C>T Substitution p.Arg225X Substitution L12 CMD1A Dilated cardiomyopathy 1A 115200 # 17609 c.673C>T Substitution p.Arg225X Substitution L12 CMD1A Dilated cardiomyopathy 1A 115200 # 13097 C.700OT Substitution p.Gln234X Substitution L12 CMD1A Dilated cardiomyopathy 1A 115200 # 13201 c.736C>T Substitution p.Gln246X Substitution 2A CMD1A Dilated cardiomyopathy 1A 115200 # 17786 C.736OT Substitution p.Gln246X Substitution 2A CMD1A Dilated cardiomyopathy 1A 115200 # 17779 c.767T>G Substitution p.Val256Gly Substitution 2A CMD1A Dilated cardiomyopathy 1A 115200 # 11809 c.800A>G Substitution p.Tyr267Cys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13173 c.800A>G Substitution p.Tyr267Cys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 11810 c.855delG Deletion p.Ala287LeufsX191 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 11613 c.908_909delCT Deletion p.Ser303CysfsX26 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 12384 c.908_909delCT Deletion p.Ser303CysfsX26 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13206 c.936+1 G>T Substitution P? Unknown Unknown CMD1A Dilated cardiomyopathy 1A 115200 # 16805 C.937-11OG Substitution p.Leu313GlyfsX31 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 8846 c.949G>A Substitution p.Glu317Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 11617 c.949G>A Substitution p.Glu317Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13175 c.949G>A Substitution p.Glu317Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13176 c.949G>A Substitution p.Glu317Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13621 c.949G>A Substitution p.Glu317Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 13100 c.952G>A Substitution p.Ala318Thr Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 £ 16956 c.952G>A Substitution p.Ala318Thr Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 11700 c.959delT Deletion p.Leu320fsX160 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 0 9409 c.959delT Deletion p.Leu320fsX160 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 KJ i© 9391 c.959delT Deletion p.Leu320fsX160 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 © 'o 14032 c.959delT Deletion p.Leu320fsX160 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 1© Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 12389 C.961OT Substitution p.Arg321X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 O 14077 c.961C>T Substitution p.Arg321X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 n 202 u 14093 C.961OT Substitution p.Arg321X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 n •1 / 0 1 17737 C.961OT Substitution p.Arg321X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 n lot U 17738 c.961C>T Substitution p.Arg321X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 oe 9155 c.976T>A Substitution p.Ser326Thr Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 11760 c.[992G>A; =]+[=; 1039G>A] Substitution p.[Arg331Glu; =]+[=; Glu347Lys] Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 11811 c.992G>C Substitution p.Arg331 Pro Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 14075 c.992G>A Substitution p.Arg331Gln Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 17477 c.1003C>T Substitution p.Arg335Trp Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 18486 c.1039G>A Substitution p.Glu347Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 9012 c.1046G>T Substitution p.Arg349Leu Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13561 c.1048G>C Substitution p.Ala350Pro Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 14204 c.1057C>A Substitution p.Gln353Lys Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 14072 c.1063C>T Substitution p.Gln355X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 17475 c.1070A>C Substitution p.Asp357Ala Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13116 c.1072G>T Substitution p.Glu358X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 9152 c.1085_1085delT Deletion p.Leu363TrpfsX117 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 17026 c.1085_1085delT Deletion p.Leu362TrpfsX117 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 16157 c.1102_1130dupGCCCTGG ACATGGAGATCCACGCCT ACCG Duplication p.Lys378ProfsX112 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 13102 c.1114delG Deletion p.Glu372ArgfsX107 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 # 8866 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 # 8869 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 n 8880 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 9160 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 cd 9162 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 © 12330 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 © Ul 13178 c.1130G>T Substitution p.Arg377Leu Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 © 4— © Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syn^ 13623 C.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 iO 14034 c.1130G>A Substitution p.Arg377His Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 J02 0 17664 c.1150G>T Substitution p.Glu384X Substitution 2B CMD1A Dilated cardiomyopathy 1A 115200 0 / 1 1 17482 c.1157+1G>T Substitution p.Arg386SerfsX21 Frame shift 2B CMD1A Dilated cardiomyopathy 1A 115200 108 0 13104 c.1163G>A Substitution p.Arg388His Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 16958 c.1163G>A Substitution p.Arg388His Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13106 C.1195OT Substitution p.Arg399Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 16960 c.1195C>T Substitution p.Arg399Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17782 c.1197_1240delTGGCCGTG CTTCCTCTCACTCATCCCA GACACAGGGTGGGGGCA Deletion p.Gly400ArgfsX11 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17789 C.1292OG Substitution p.Ser431X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14082 c.1294C>T Substitution p.Gln432X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14084 c.1294C>T Substitution p.Gln432X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14085 c.1294C>T Substitution p.Gln432X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14086 c.1294C>T Substitution p.Gln432X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13108 c.1307_1308insGCAC Insertion p.Ser437HisfsX1 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 # 16962 c.1307_1308insGCAC Insertion p.Ser437HisfsX1 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14088 c.1318G>A Substitution p.Val440Met Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14090 c.1318G>A Substitution p.Val440Met Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14091 c.1318G>A Substitution p.Val440Met Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 11812 c.1370delA Deletion p.Lys457SerfsX21 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 # 12397 c.1380+1 G>A Substitution P? Unknown Unknown CMD1A Dilated cardiomyopathy 1A 115200 # 9413 c.1397_1397delA Deletion p.Asn466llefsX14 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 # 9161 c.1397_1397delA Deletion p.Asn466llefsX14 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 13110 c.1412G>A Substitution p.Arg471His Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 16973 c.1412G>A Substitution p.Arg471His Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 13112 c.1424_1425insAGA Insertion p.Gly474_Asp475insGlu Insertion Tail CMD1A Dilated cardiomyopathy 1A 115200 .NJ 11508 c.1443C>G Substitution p.Tyr481X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 17791 c.1443C>G Substitution p.Tyr481X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 io 17480 c.1489-1 G>T Substitution p.lle497_Glu536del Deletion Tail CMD1A Dilated cardiomyopathy 1A 115200 <3 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syrr^ 13180 c.1492T>A Substitution p.Trp498Arg Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 L O I 9153 c.1493_1493delG Deletion p.Ala499LeufsX47 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 I ►02: 12395 c.1512_1513insAG Insertion p.Thr505ArgfsX44 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 17784 c.1526_1527insC Insertion p.Thr510TyrfsX42 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 L08* 17797 c.1526_1527insA Insertion p.Thr510TyrfsX42 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 17486 c.1549C>T Substitution p.Gln517X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17484 c.1560G>A Substitution p.Trp520X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13625 c.1567G>A Substitution p.Gly523Arg Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 11624 c.1579_1580insCTGC Insertion p.Arg527ProfsX26 Frame shift Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17558 c.1583C>T Substitution p.Thr528Met Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 9307 C.1621OT Substitution p.Arg541 Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 9283 C.1621OA Substitution p.Arg541Ser Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 9151 C.1621OA Substitution p.Arg541Ser Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13592 C.1621OT Substitution p.Arg541 Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14202 C.1621OA Substitution p.Arg541Ser Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 16472 c.1621C>G Substitution p.Arg541Gly Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17774 C.1621OT Substitution p.Arg541 Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17775 C.1621OT Substitution p.Arg541 Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13559 c.1622G>A Substitution p.Arg541His Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 9392 C.1718OT Substitution p.Ser573Leu Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13182 C.1718OT Substitution p.Ser573Leu Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 13183 C.1718OT Substitution p.Ser573Leu Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 14038 c.1718C>T Substitution p.Ser573Leu Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # 17667 c.1879C>T Substitution p.Arg624Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 % _ 13565 c.1904G>A Substitution p.Gly635Asp Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 8833 c.1930C>T Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 9018 c.1930C>T Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 Cj 11500 c.1930C>T Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 11501 c.1930C>T Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 11502 C.1930OA Substitution p.Arg644His Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sym]^ 13185 C.1930OT Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 * KJ 13337 c.1930C>T Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # s 14080 c.1930C>T Substitution p.Arg644Cys Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # ® 13114 c.1960C>T Substitution p.Arg654X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 # oc 16964 c.1960C>T Substitution p.Arg654X Substitution Tail CMD1A Dilated cardiomyopathy 1A 115200 #00 11788 c.? Unknown p.Tyr481X Substitution Tail DCM-CD Dilated cardiomyopathy with conduction system defects - - 17886 c.80C>T Substitution p.Thr27lle Substitution Head DCM-CD Dilated cardiomyopathy with conduction system defects - - 13486 C.106OT Substitution p.Gln36X Substitution 1A DCM-CD Dilated cardiomyopathy with conduction system defects - - 11792 c.158A>T Substitution p.Glu53Val Substitution 1A DCM-CD Dilated cardiomyopathy with conduction system defects - - 18301 C.175OG Substitution p.Leu59Val Substitution 1A DCM-CD Dilated cardiomyopathy with conduction system defects - - 11791 c.481G>A Substitution p.Glu161Lys Substitution 1B DCM-CD Dilated cardiomyopathy with conduction system defects - - 13204 C.514-1G>A Substitution P? Unknown Unknown DCM-CD Dilated cardiomyopathy with conduction system defects - - 11793 c.556G>A Substitution p.Glu186Lys Substitution 1B DCM-CD Dilated cardiomyopathy with conduction system defects - - 11789 c.568C>T Substitution p.Arg190Trp Substitution 1B DCM-CD Dilated cardiomyopathy with conduction system defects - - 11787 c.575A>G Substitution p.Asp192Gly Substitution 1B DCM-CD Dilated cardiomyopathy with conduction system defects - - 18470 C.683A>T Substitution p.Glu228Val Substitution L12 DCM-CD Dilated cardiomyopathy with conduction system defects - - 17868 c.871G>A Substitution p.Glu291Lys Substitution 2B DCM-CD Dilated cardiomyopathy with conduction system defects - - 17870 c.949G>A Substitution p.Glu317Lys Substitution 2B DCM-CD Dilated cardiomyopathy with conduction system defects - PCT / 1 13078 c.1069G>C Substitution p.Asp357His Substitution 2B DCM-CD Dilated cardiomyopathy with conduction system defects - SG2( 1 13208 C.1157+1G>A Substitution P? Unknown Unknown DCM-CD Dilated cardiomyopathy with conduction system defects - )20 / 0: 1 18490 c.1412G>A Substitution p.Arg471His Substitution Tail DCM-CD Dilated cardiomyopathy with conduction system defects - UI © - 4— © Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syr^ 1 11814 c.1526_1527insC Insertion p.Thr510TyrfsX42 Frame shift Tail DCM-CD Dilated cardiomyopathy with conduction system defects - o © 9008 C.1621OT Substitution p.Arg541 Cys Substitution Tail DCM-CD Dilated cardiomyopathy with conduction system defects - 1 21 / 01 17578 C.1711OA Substitution P = Silent Not affected DCM-CD Dilated cardiomyopathy with conduction system defects - 0898 17880 C.1930OT Substitution p.Arg644Cys Substitution Tail DCM-CD Dilated cardiomyopathy with conduction system defects - - 18305 c.1774G>A Substitution p.Gly592Arg Substitution Tail DAPJ Distal acroosteolysis, poikiloderma and joint stiffness - - 13581 C.1930OT Substitution p.Arg644Cys Substitution Tail - Distal motor neuropathy - - 17813 c.93G>C Substitution p.Glu31Asp Substitution Head - Dropped head syndrome - - 9020 c.94_96delAAG Deletion p.Lys32del Deletion 1A - Dropped head syndrome - - 13476 c.116A>G Substitution p.Asn39Ser Substitution 1A - Dropped head syndrome - - 13466 c.149G>C Substitution p.Arg50Pro Substitution 1A - Dropped head syndrome - - 13464 C.745OT Substitution p.Arg249Trp Substitution 2A - Dropped head syndrome - - 13470 c.905T>C Substitution p.Leu302Pro Substitution 2B - Dropped head syndrome - - 13468 c.1072G>A Substitution p.Glu358Lys Substitution 2B - Dropped head syndrome - - 13482 c.1072G>A Substitution p.Glu358Lys Substitution 2B - Dropped head syndrome - - 13484 c.1072G>A Substitution p.Glu358Lys Substitution 2B - Dropped head syndrome - - 13474 c.1358G>C Substitution p.Arg453Pro Substitution Tail - Dropped head syndrome - - 13472 c.1364G>C Substitution p.Arg455Pro Substitution Tail - Dropped head syndrome - - 13478 c.1366A>G Substitution p.Asn456Asp Substitution Tail - Dropped head syndrome - - 13480 c.1381-2A>G Substitution P? Unknown Unknown - Dropped head syndrome - - 11652 c.-3_12delGCCATGGAGACCC CG Deletion p.Met1_Pro4del Deletion Head EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # ■O 8743 C.16OT Substitution p.Gln6X Substitution Head EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 CT / S 8796 c.16C>T Substitution p.Gln6X Substitution Head EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 G202 11746 c.31delC Deletion p.Arg11AlafsX85 Frame shift Head EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 :0 / 05( 9262 c.73C>G Substitution p.Arg25Gly Substitution Head EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 )407 Database ID cDNA Variant cDNA Variant Tvoes Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Svm^ 9376 c.74G>C Substitution p.Arg25Pro Substitution Head EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 o #N> © 9177 c.94_96delAAG Deletion p.Lys32del Deletion 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 21 / 01 ft 8998 c.94_96delAAG Deletion p.Lys32del Deletion 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0898 ft 9014 c.94_96delAAG Deletion p.Lys32del Deletion 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13594 c.98A>G Substitution p.Glu33Gly Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11747 c.99G>C Substitution p.Glu33Asp Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8999 C.103OG Substitution p.Leu35Val Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11748 c.116A>G Substitution p.Asn39Ser Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16329 c.116A>G Substitution p.Asn39Ser Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 18174 c.116A>G Substitution p.Asn39Ser Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9377 c.127G>A Substitution p.Ala43Thr Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8797 c.134A>G Substitution p.Tyr45Cys Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16331 c.134A>G Substitution p.Tyr45Cys Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13605 c.136A>G Substitution p.lle46Val Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13545 c.139G>C Substitution p.Asp47His Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9378 c.148C>A Substitution p.Arg50Ser Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 PCT % 8798 c.149G>C Substitution p.Arg50Pro Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 / SG2 % 8799 c.188T>G Substitution p.lle63Ser Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # © 9175 C.188T>A Substitution p.lle63Asn Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 ►5040 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syrr^ 11633 c.188T>A Substitution p.lle63Asn Substitution 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 ofo I 13192 c.203_208delAGGTGG Deletion p.Glu68_Val69del Deletion 1A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 I 21 / 01 -K 12477 c.265C>T Substitution p.Arg89Cys Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 8680 1 13596 c.265C>T Substitution p.Arg89Cys Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 17193 c.266G>T Substitution p.Arg89Leu Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9410 c.334_336delGAG Deletion p.Glu112del Deletion 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9000 c.334_336delGAG Deletion p.Glu112del Deletion 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16291 C.357OT Substitution P = Silent Not affected EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 17182 c.367_369delAAG Deletion p.Lys123del Deletion 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9379 c.398G>C Substitution p.Arg133Pro Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11632 c.419T>C Substitution p.Leu140Pro Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9015 c.428C>T Substitution p.Ser143Phe Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 12609 c.428C>T Substitution p.Ser143Phe Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8795 c.448A>C Substitution p.Thr150Pro Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16334 c.448A>C Substitution p.Thr150Pro Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13453 c.485T>C Substitution p.Leu162Pro Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 Q 16396 c.566_567delGGinsCC Indel p.Arg189Pro Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 i r / SG: ■« 16299 c.568_570dupCGG Duplication p.Arg190dup Duplication 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 2020 / 9380 c.588_596delGCTGCAGAC Deletion p.Argl 96_Thr199delinsS er Indel 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 1 0504( Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sym^ 16301 C.618OG Substitution p.Phe206Leu Substitution 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 U #N> o 12382 c.625delA Deletion p.Asn209ThrfsX271 Frame shift 1B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 ft HO / TZ 8800 c.665A>C Substitution p.His222Pro Substitution L12 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0898 ft 13547 c.694G>C Substitution p.Gly232Arg Substitution L12 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8801 c.695G>A Substitution p.Gly232Glu Substitution L12 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 12485 c.695G>A Substitution p.Gly232Glu Substitution L12 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9001 c.743T>C Substitution p.Leu248Pro Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16336 C.745OT Substitution p.Arg249Trp Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16337 c.745C>T Substitution p.Arg249Trp Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16338 C.745OT Substitution p.Arg249Trp Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16342 c.[745C>T; 1930OT] Substitution p.[Arg249Trp; Arg644Cys] Substitution 2A, Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8783 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11380 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11381 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8802 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9002 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 9023 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 GT 11631 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 020 / 0 % 11749 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 5040' % Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Svm^ 11750 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 O #N> © 13552 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 21 / 01 % 16344 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0898 ft 16345 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 18176 c.746G>A Substitution p.Arg249Gln Substitution 2A EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11751 c.775T>G Substitution p.Tyr259Asp Substitution L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9640 c.781_783delAAG Deletion p.Lys261del Deletion L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9411 c.781_783delAAG Deletion p.Lys261del Deletion L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9381 c.781_783delAAG Deletion p.Lys261del Deletion L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13584 c.781_783delAAGinsGTGG AGCAGTATAAGAAA Indel p.Lys261delinsValGluGI nTyrLysLys Indel L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16149 c.788T>C Substitution p.Leu263Pro Substitution L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 17403 c.788T>C Substitution p.Leu263Pro Substitution L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 17751 c.788T>C Substitution p.Leu263Pro Substitution L2 EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 17405 c.799T>C Substitution p.Tyr267His Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9003 c.800A>G Substitution p.Tyr267Cys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11809 c.800A>G Substitution p.Tyr267Cys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 PC % 13173 C.800A>G Substitution p.Tyr267Cys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 r / SG: ft 16303 c.802T>C Substitution p.Ser268Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 IM o 16305 C.810G>A Substitution P = Silent Not affected EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0504( ft Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Symt^ 16307 c.810G>A Substitution P = Silent Not affected EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 © # y o 16309 c.810+1G>A Substitution P? Unknown Unknown EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 n / on % 16347 C.812T>C Substitution p.Leu271Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0898 18186 c.832G>C Substitution p.Ala278Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8803 c.881A>C Substitution p.Gln294Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16349 c.881A>C Substitution p.Gln294Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16311 c.883T>C Substitution p.Ser295Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8863 C.907T>C Substitution p.Ser303Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16351 c.907T>C Substitution p.Ser303Pro Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8786 c.1007G>A Substitution p.Arg336Gln Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16314 c.1064_1066delAGC Deletion p.Gln355del Deletion 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8804 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11388 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11816 C.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9167 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11478 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 -Q #o 11479 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 7SG2 % 11480 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 © 11752 C.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 )5040 Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syn^ 12479 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 <2 © 12483 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 13598 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 © go 13603 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16353 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16354 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16355 c.1072G>A Substitution p.Glu358Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16316 c.1081G>A Substitution p.Glu361Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8806 c.1112T>A Substitution p.Met371 Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 18184 c.1124C>G Substitution p.Ala375Gly Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11634 c.1130G>T Substitution p.Arg377Leu Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11693 c.1130G>A Substitution p.Arg377His Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 12405 c.1130G>A Substitution p.Arg377His Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 18223 c.1130G>A Substitution p.Arg377His Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 12474 c.1142A>C Substitution p.Glu381Ala Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11629 c.1157G>A Substitution p.Arg386Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 13653 c.1157G>T Substitution p.Arg386Met Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 16357 c.1157G>A Substitution p.Arg386Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 l / OZOi I 16358 c.1157G>A Substitution p.Arg386Lys Substitution 2B EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 I I 55040 n Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Svm^ 16319 c.1158-2A>G Substitution P? Unknown Unknown EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 O #N> © 11817 c.1162C>T Substitution p.Arg388Cys Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 21 / 01 % 9281 c.1187A>G Substitution p.Gln396Arg Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0898 ft 8862 c.1201C>T Substitution p.Arg401Cys Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9176 C.1201OT Substitution p.Arg401Cys Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9302 c.1201C>T Substitution p.Arg401Cys Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9004 c.1337A>T Substitution p.Asp446Val Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16321 c.1346G>A Substitution p.Gly449Asp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 18192 c.1346G>T Substitution p.Gly449Val Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8744 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8787 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11382 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11383 C.1357OT Substitution p.Arg453Trp Substitution Tail ED MD 2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11384 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 8807 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 11389 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 PCI 11390 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 r / SG: ft 8836 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 IM o 9005 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 0504( ft Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Symbol 9304 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 )202 % 11614 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 2 11753 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 oc a 12481 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13590 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13607 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13609 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 13611 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16363 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16364 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16365 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16366 C.1357OT Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16367 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16368 c.1357C>T Substitution p.Arg453Trp Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16323 C.1361T>C Substitution p.Leu454Pro Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 9513 C.1367A>T Substitution p.Asn456lle Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 TCI % 8810 C.1368OA Substitution p.Asn456Lys Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 7SG2 % 11318 c.1368_1370delCAA Deletion p.Asn456del Deletion Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 :020 / ( % 17446 c.1368_1370delCAA Deletion p.Asn456del Deletion Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 )5040 % Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim S'^pbp! 17447 c.1368_1370delCAA Deletion p.Asn456del Deletion Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 <! O 16370 c.1381-2A>G Substitution P? Unknown Unknown EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 m 021 / 0 1 16372 c.[1381-1G>T; 1381G>T] Substitution p.[?; Asp461Tyr] Unknown, Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 m 1089: 1 16325 c.1399T>C Substitution p.Trp467Arg Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 8791 c.1406T>C Substitution p.lle469Thr Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 18194 c.1466T>C Substitution p.Leu489Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 16327 c.1488+1G>A Substitution P? Unknown Unknown EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 13180 c.1492T>A Substitution p.Trp498Arg Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 16375 c.1526dupC Duplication p.Thr510TyrfsX42 Frame shift Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 18188 C.1540T>A Substitution p.Trp514Arg Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 18190 c.1540T>A Substitution p.Trp514Arg Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 12434 c.1558T>G Substitution p.Trp520Gly Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 18179 c.1558T>C Substitution p.Trp520Arg Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 8811 c.1559G>C Substitution p.Trp520Ser Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 8745 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 11344 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 ■0 n 8792 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 m 7SG2 1 8812 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 n •020 / 1 1 11391 C.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 n )5040 1 1 Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 8838 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 o 8859 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 I ►21 / 0] 1 11423 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 n «6801 1 11630 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 11754 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 16377 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 18182 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 8793 c.1583C>A Substitution p.Thr528Lys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 8814 c.1583C>A Substitution p.Thr528Lys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 11392 c.1583C>A Substitution p.Thr528Lys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 9006 c.1583C>G Substitution p.Thr528Arg Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16379 c.1583C>A Substitution p.Thr528Lys Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16381 c.1583C>G Substitution p.Thr528Arg Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16382 c.1583C>G Substitution p.Thr528Arg Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 16407 c.1583C>G Substitution p.Thr528Arg Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 # 18196 c.1583C>G Substitution p.Thr528Arg Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 PCT; 18297 C.1588OT Substitution p.Leu530Phe Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 1 'SG2( 1 8747 c.1589T>C Substitution p.Leu530Pro Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 1 )20 / 0 1 16384 c.1621C>A Substitution p.Arg541Ser Substitution Tail EDMD2 Emery-Dreifuss muscular dystrophy, autosomal dominant 181350 1 1 5040] 1 1 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sy^-Tl 9007 c.1622G>A Substitution p.Arg541His Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 o is) 16387 c.1622G>C Substitution p.Arg541 Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 n O / IZC I 13588 C.1633OT Substitution p.Arg545Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 I I 10891 1 16389 c.1804G>A Substitution p.Arg541 Pro Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 9383 c.1871G>A Substitution p.Arg624His Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 9154 c.1930C>T Substitution p.Arg644Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 13570 C.1930OT Substitution p.Arg644Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 13571 c.1930C>T Substitution p.Arg644Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 13572 C.1930OT Substitution p.Arg644Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 13573 C.1930OT Substitution p.Arg644Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 16392 C.1930OT Substitution p.Arg644Cys Substitution Tail EDMD2 Emery-Dre if uss muscular dystrophy, autosomal dominant 181350 # 9523 C.664OT Substitution p.His222Tyr Substitution L12 EDMD3 Emery-Dre if uss muscular dystrophy, autosomal recessive 604929 # 17407 c.674G>A Substitution p.Arg225Gln Substitution L12 EDMD3 Emery-Dre if uss muscular dystrophy, autosomal recessive 604929 # 17573 c.1445G>A Substitution p.Arg482Gln Substitution Tail EDMD3 Emery-Dre if uss muscular dystrophy, autosomal recessive 604929 # 13319 c.1580G>C Substitution p.Arg527Pro Substitution Tail EDMD3 Emery-Dre if uss muscular dystrophy, autosomal recessive 604929 # 18345 C.? Unknown p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 ■0 8847 C.82OT Substitution p.Arg28T rp Substitution Head FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 r / SG 1 18291 c.139G>A Substitution p.Asp47Asn Substitution 1A FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 2020 / 1 8861 C.178OG Substitution p.Arg60Gly Substitution 1A FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 0504i 1 1 o Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 14260 C.178OG Substitution p.Arg60Gly Substitution 1A FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 o 8848 C.184OG Substitution p.Arg62Gly Substitution 1A FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I I 121 / 01 1 14256 C.184OG Substitution p.Arg62Gly Substitution 1A FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 L0898 1 12100 c.398G>T Substitution p.Arg133Leu Substitution 1B FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 14258 c.575A>T Substitution p.Asp192Val Substitution 1B FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17624 c.667G>A Substitution p.Glu223Lys Substitution L12 FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11775 C.688G>A Substitution p.Asp230Asn Substitution L12 FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11776 C.1195C>T Substitution p.Arg399Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17066 c.1232G>A Substitution p.Gly411Asp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12096 C.1315C>T Substitution p.Arg439Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17208 C.1315C>T Substitution p.Arg439Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11542 c.[1318G>A; =]+[=; 1445G>A] Substitution p.[Val440Met; =]+[=; Arg482Gln] Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8781 c.1394G>A Substitution p.Gly465Asp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12601 C.1411C>G Substitution p.Arg471Gly Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8754 C.1444C>T Substitution p.Arg482T rp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11358 C.1444C>T Substitution p.Arg482T rp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 PCT / 1 11359 C.1444C>T Substitution p.Arg482T rp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 SG2C 1 11360 C.1444C>T Substitution p.Arg482T rp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 120 / Of 1 11361 C.1444C>T Substitution p.Arg482T rp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 n Z.OTOS 1 1 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Symkl' 11362 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 O 2C 11363 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I21 / 01 11364 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 L0898 11365 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8773 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11374 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11375 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11376 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11377 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11378 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11379 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8816 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11393 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11394 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11395 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11396 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 PCT / 11397 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 SG2C 8834 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 KJ #5 © 9213 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 50407 Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 9156 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 o 11543 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I 121 / 01 1 11544 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 L0898 1 11662 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11692 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11699 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12101 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12102 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12103 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12104 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12105 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 14066 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16433 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16434 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16682 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17866 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 PCT / 1 17195 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 SG2C 1 17464 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 120 / Of 1 17465 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 n Z.OTOS 1 1 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sy>-oj 17466 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 o bJ 17467 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 b5 © 17733 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I I 1089f I 17735 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17744 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17936 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 18484 C.1444OT Substitution p.Arg482Trp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8753 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11354 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11355 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11356 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11357 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8763 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8764 c.1445G>T Substitution p.Arg482Leu Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8768 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11370 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 ■0 n 11371 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I I VSG2 I 11372 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I I :020 / ( I 11373 C.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I I )5040 I I Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sy^oI 8822 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 O KJ 8868 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 KJ © 9305 c.1445G>T Substitution p.Arg482Leu Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 I I 10891 1 11663 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11667 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12098 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12387 c.1445G>A Substitution p.Arg482Gln Substitution Unknown FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12418 c.1445G>A Substitution p.Arg482Gln Substitution Unknown FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12423 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 13150 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 13367 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16285 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16436 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16437 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16438 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16439 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 ■O Q 16440 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 r / SG: 1 18138 c.1445G>A Substitution p.Arg482Gln Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 2020 / 1 8765 c.1458G>C Substitution p.Lys486Asn Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 1 0504( 1 1 Substitte Sheet (Rule 26) 00 O Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sy^ol 11366 c.1458G>C Substitution p.Lys486Asn Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 o 8767 c.1458G>T Substitution p.Lys486Asn Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 n 0 / 17( 1 9319 c.1488+5G>C Substitution p.lle497_Met664delinsVal ThrGlyArgAlaLeuGlyThrL euGlyArgProT rpValAlaMe tGlyAlaLeuGlyX Indel Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 1 10898 1 17455 c.1683G>C Substitution P = Silent Not affected FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11777 C.1718OT Substitution p.Ser573Leu Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 8780 c.1745G>A Substitution p.Arg582His Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16429 c.1745G>A Substitution p.Arg582His Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16430 c.1745G>A Substitution p.Arg582His Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 16431 c.1745G>A Substitution p.Arg582His Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 9452 c.1751G>A Substitution p.Arg584His Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 11545 c.1751G>A Substitution p.Arg584His Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 12429 c.1772G>T Substitution p.Arg156Cys Substitution 1B FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 17068 c.1892G>A Substitution p.Gly631Asp Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 13575 C.1930OT Substitution p.Arg644Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 # 13576 C.1930OT Substitution p.Arg644Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 ■O n 13579 C.1930OT Substitution p.Arg644Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 Ci 17461 C.1930OT Substitution p.Arg644Cys Substitution Tail FPLD2 Familial partial lipodystrophy (Dunnigan type) 151660 n 0707 1 12601 C.1411OG Substitution p.Arg471Gly Substitution Tail FPLD1 Familial partial lipodystrophy (Kobberling) 608600 1 / 0504 1 © Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 11482 c.[1583C>T; =]+[=; 1748OT] Substitution p.[Thr528Met; =]+[=; Ser583Leu] Substitution Tail FPLD1 Familial partial lipodystrophy (Kbbberling) 608600 o NJ 9183 C.1748OT Substitution p.Ser583Leu Substitution Tail FPLD1 Familial partial lipodystrophy (Kbbberling) 608600 I I )21 / 0 1 11481 C.1748OT Substitution p.Ser583Leu Substitution Tail FPLD1 Familial partial lipodystrophy (Kbbberling) 608600 1 1 10895 13490 C.29OT Substitution p.ThrlOlle Substitution Head - Generalized lipoatrophy syndrome - 8867 c.398G>T Substitution p.Arg133Leu Substitution 1B - Generalized lipoatrophy syndrome - - 17762 c.1609-12T>G Substitution p.Glu536fsX14 Frame shift Tail HSS Hallermann-Streiff syndrome 234100 % 17260 c.1930C>T Substitution p.Arg644Cys Substitution Tail HSS Hallermann-Streiff syndrome 234100 % 13153 c.1609-12T>G Substitution p.Glu536fsX14 Frame shift Tail - Heart-hand syndrome, Slovenian Type 610140 % 14097 C.11OG Substitution p.Pro4Arg Substitution Head HGPS Hutchinson-Gilford progeria syndrome 176670 # 14112 C.11OG Substitution p.Pro4Arg Substitution Head HGPS Hutchinson-Gilford progeria syndrome 176670 # 9172 c.29C>T Substitution p.ThrlOlle Substitution Head HGPS Hutchinson-Gilford progeria syndrome 176670 # 14108 c.29C>T Substitution p.ThrlOlle Substitution Head HGPS Hutchinson-Gilford progeria syndrome 176670 # 14110 c.29C>T Substitution p.ThrlOlle Substitution Head HGPS Hutchinson-Gilford progeria syndrome 176670 # 14101 c.331G>T Substitution p.Glu111Lys Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 # 14095 c.406G>C Substitution p.Asp136His Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 # 17070 c.412G>A Substitution p.Glu138Lys Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 # 9016 C.428OT Substitution p.Ser143Phe Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 # 12609 C.428OT Substitution p.Ser143Phe Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 PCI 8871 c.433G>A Substitution p.Glu145Lys Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 n 1 14106 c.475G>A Substitution p.Glu159Lys Substitution 1B HGPS Hutchinson-Gilford progeria syndrome 176670 n 0 / 07(1 1 17626 c.899A>G Substitution p.Asp300Gly Substitution 2B HGPS Hutchinson-Gilford progeria syndrome 176670 1 1 5040' 1 1 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 21 17903 c.917T>G Substitution p.Leu306Arg Substitution 2B HGPS Hutchinson-Gilford progeria syndrome 176670 d © 14114 C.1303OT Substitution p.Arg435Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 bU © 9393 C.1411OT Substitution p.Arg471Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 © oe © go 12615 C.1411OT Substitution p.Arg471Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 9394 c.1579C>T Substitution p.Arg527Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 13119 c.1579C>T Substitution p.Arg527Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 13651 c.1579C>T Substitution p.Arg527Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11671 c.[1583C>T; =]+[=; 1619T>C] Substitution p.[Thr528Met; =]+[=; Met540Thr] Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 9013 c.1626G>C Substitution p.Lys542Asn Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 9173 c.1733A>T Substitution p.Glu578Val Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 14099 c.1762T>C Substitution p.Cys588Arg Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 14104 c.1762T>C Substitution p.Cys588Arg Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11785 c.1821G>A Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 9527 c.1822G>A Substitution p.Gly608Ser Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 8876 c.1822G>A Substitution p.Gly608Ser Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 9396 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 PCT 9398 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 1 1 / SG2 1 11428 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 1 1 020 / C 1 11429 C.1824OT Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 1 1 15040 1 1 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim. Symt^ 11430 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 )202 11431 C.1824OT Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 1 / 010 11432 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 % 868 11433 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11434 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11435 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11436 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11437 C.1824OT Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11438 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11439 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11440 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11441 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11442 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11443 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 11444 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # ■Q 9395 C.1824OT Substitution P? Unknown Unknown HGPS Hutchinson-Gilford progeria syndrome 176670 CT / S it 11449 c.1824C>T Substitution P? Unknown Unknown HGPS Hutchinson-Gilford progeria syndrome 176670 # s © 11450 c.1824C>T Substitution P? Unknown Unknown HGPS Hutchinson-Gilford progeria syndrome 176670 © # © Ui 11451 c.1824C>T Substitution P? Unknown Unknown HGPS Hutchinson-Gilford progeria syndrome 176670 © # 5 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sms' 11452 c.1824C>T Substitution P? Unknown Unknown HGPS Hutchinson-Gilford progeria syndrome 176670 I I / O 20 % 9171 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 i                                           i >21 / 03 % 9017 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 86801 । । 9019 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 12074 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 12075 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 12076 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 12085 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 12354 c.1824C>T Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 13533 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 # 17393 c.1824C>T Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 17395 c.1824C>T Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 17564 c.1824C>T Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 17729 c.1824C>T Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 17818 c.1824C>T Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 # 9009 C.1868OG Substitution p.[Thr623Ser, Val622 Gln656del] Deletion, Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 1 1 PCT / % 12457 C.1868OG Substitution p.[Thr623Ser, Val622 Gln656del] Deletion, Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 i i SG20 % 9174 c.1930C>T Substitution p.Arg644Cys Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 ;o7ozi । । 11615 c.1960C>T Substitution p.Arg654X Substitution Tail HGPS Hutchinson-Gilford progeria syndrome 176670 । । 50407 % Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syn*: ■ 17159 c.1968G>A Substitution P = Silent Not affected HGPS Hutchinson-Gilford progeria syndrome 176670 ofb / i 11784 c.1968+1 G>A Substitution p.Val607_Gln656del Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 i I21 / 01 -K 17161 c.1968+5G>A Substitution p.Val607_Gln656del Deletion Tail HGPS Hutchinson-Gilford progeria syndrome 176670 86801 1 12615 C.1411OT Substitution p.Arg471Cys Substitution Tail - Lamin-related rigid spine muscular dystrophy - - 17426 c.31delC Deletion p.Arg11AlafsX85 Frame shift Head LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 14254 c.73C>G Substitution p.Arg25Gly Substitution Head LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17886 c.80C>T Substitution p.Thr27lle Substitution Head LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 18488 c.80C>T Substitution p.Thr27lle Substitution Head LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17428 c.99G>C Substitution p.Glu33Asp Substitution 1A LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17429 c.99G>C Substitution p.Glu33Asp Substitution 1A LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17430 c.99G>C Substitution p.Glu33Asp Substitution 1A LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17434 c.194A>G Substitution p.Glu65Gly Substitution 1A LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17435 c.194A>G Substitution p.Glu65Gly Substitution 1A LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 16283 c.302G>C Substitution p.Arg101Pro Substitution 1B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17399 c.388G>T Substitution p.Ala130Ser Substitution 1B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17755 c.388G>T Substitution p.Ala130Ser Substitution 1B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 1 PCT / -K 17432 c.471G>A Substitution P = Silent Not affected LGMD1B Limb-girdle muscular dystrophy type 1B 159001 K9S 1 9216 c.513G>A Substitution P = Silent Not affected LGMD1B Limb-girdle muscular dystrophy type 1B 159001 ;o7oa i 17575 c.513+1G>A Substitution P? Unknown Unknown LGMD1B Limb-girdle muscular dystrophy type 1B 159001 i i 50407 -K Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim 17437 C.565OT Substitution p.Arg189Trp Substitution 1B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 I I / O 20 % 9639 c.622_624delAAG Deletion p.Lys208del Deletion 1B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 I                                           I 12403 c.624_626delGAA Deletion p.Lys208del Deletion 1B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 86801 । i 16145 c.673C>T Substitution p.Arg225X Substitution L12 LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17401 c.673C>T Substitution p.Arg225X Substitution L12 LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17753 c.673C>T Substitution p.Arg225X Substitution L12 LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 13555 c.746G>A Substitution p.Arg249Gln Substitution 2A LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 9164 c.777T>A Substitution p.Tyr259X Substitution L2 LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 12401 c.777T>A Substitution p.Tyr259X Substitution L2 LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17760 c.777T>A Substitution p.Tyr259X Substitution L2 LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 11810 c.855delG Deletion p.Ala287LeufsX191 Frame shift 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 9021 c.864_867delCCAC Deletion p.His289ArgfsX190 Frame shift 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 11759 c.864_867delCCAC Deletion p.His289ArgfsX190 Frame shift 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 12384 c.908_909delCT Deletion p.Ser303CysfsX26 Frame shift 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 11811 c.992G>C Substitution p.Arg331 Pro Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 18309 c.1001_1003delGCC Deletion p.Ser334del Deletion 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 1 1 PCT / % 8794 c.1130G>A Substitution p.Arg377His Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 i i SG20 % 8850 c.1130G>T Substitution p.Arg377Leu Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 ;o7ozi । । 9301 c.1130G>A Substitution p.Arg377His Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 । । 50407 % Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Sym< 9024 c.1130G>T Substitution p.Arg377Leu Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 I I / O 20 ft 11762 c.1130G>A Substitution p.Arg377His Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 I                                           I 13557 c.1130G>A Substitution p.Arg377His Substitution 2B LGMD1B Limb-girdle muscular dystrophy type 1B 159001 86801 । । 11755 C.1146OT Substitution P = Silent Not affected LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 11756 c.1357C>T Substitution p.Arg453Trp Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17443 c.1357C>T Substitution p.Arg453Trp Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 11812 c.1370delA Deletion p.Lys457SerfsX21 Frame shift Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17441 c.1380+1G>A Substitution P? Unknown Unknown LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 8839 c.1441T>C Substitution p.Tyr481His Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 13376 c.1488+5G>A Substitution P? Unknown Unknown LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 9181 c.1494G>T Substitution p.Trp498Cys Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 9158 c.1494G>T Substitution p.Trp498Cys Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 16442 c.1494G>T Substitution p.Trp498Cys Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 9159 c.1535T>C Substitution p.Leu512Pro Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 11763 c.1535T>C Substitution p.Leu512Pro Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 # 17449 c.1535T>C Substitution p.Leu512Pro Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 1 1 PCT / ft 17452 c.1535T>C Substitution p.Leu512Pro Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 i i SG20 ft 11758 c.1583C>A Substitution p.Thr528Lys Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 ;o7ozi । । 13446 c.1608+1G>A Substitution P? Unknown Unknown LGMD1B Limb-girdle muscular dystrophy type 1B 159001 । । 50407 ft Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Symb(-£ 9412 c.1608+5G>C Substitution p.Glu537ValfsX36 Frame shift Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 / O 20 % 13151 C.1609-3OG Substitution p.? Unknown Unknown LGMD1B Limb-girdle muscular dystrophy type 1B 159001 >21 / 03 % 11764 C.1718OT Substitution p.Ser573Leu Substitution Tail LGMD1B Limb-girdle muscular dystrophy type 1B 159001 L0898 % 13505 c.373G>A Substitution p.Gly125Ser Substitution 1B LAF Lone atrial fibrillation - - 13509 c.[373G>A; =]+[=; 1243G>A] Substitution p.[Gly125Ser; =]+[=; Val415lle] Substitution 1B, Tail LAF Lone atrial fibrillation - - 13492 C.810+63OA Substitution p.? Unknown Unknown LAF Lone atrial fibrillation - - 13495 c.937-46A>G Substitution p.? Unknown Unknown LAF Lone atrial fibrillation - - 13501 c.1149G>A Substitution P = Silent Not affected LAF Lone atrial fibrillation - - 13497 c.1158-44C>T Substitution p.? Unknown Unknown LAF Lone atrial fibrillation - - 13499 c.1158-44C>T Substitution p.? Unknown Unknown LAF Lone atrial fibrillation - - 13507 c.1243G>A Substitution p.Val415lle Substitution Tail LAF Lone atrial fibrillation - - 13511 C.1462A>C Substitution p.Thr488Pro Substitution Tail LAF Lone atrial fibrillation - - 13503 c.1803C>T Substitution P = Silent Not affected LAF Lone atrial fibrillation - - 11783 c.176T>G Substitution p.Leu59Arg Substitution 1A MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 18470 c.683A>T Substitution p.Glu228Val Substitution L12 MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 12380 c.[1318G>A; =]+[=; 1580G>A] Substitution p.[Val440Met; =]+[=; Arg527His] Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 12615 C.1411OT Substitution p.Arg471Cys Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 13119 C.1579OT Substitution p.Arg527Cys Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 17878 C.1579OT Substitution p.Arg527Cys Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # O 8851 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 KJ # o KJ 11419 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # S O 11420 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 107 Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Symb-i 11421 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 / O 20 11422 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 >21 / 03 8877 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 © if oc go 11453 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 8995 c.1580G>A Substitution p.Arg527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 9224 c.1580G>A Substitution p.Ala527His Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 17602 c.1580G>T Substitution p.Arg527Leu Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 17603 c.1580G>T Substitution p.Arg527Leu Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 17747 c.1580G>T Substitution p.Arg527Leu Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 17748 c.1580G>T Substitution p.Arg527Leu Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 12598 c.1585G>A Substitution p.Ala529Thr Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 9317 C.1586OT Substitution p.Ala529Val Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 18478 c.1620G>A Substitution p.Met540lle Substitution Tail MADA Mandibuloacral dysplasia with type A lipodystrophy 248370 # 13054 C.82OT Substitution p.Arg28Trp Substitution Head - Metabolic syndrome - - 13056 C.274C>T Substitution p.Leu92Phe Substitution 1B - Metabolic syndrome - - 13059 C.1159OG Substitution p.Leu387Val Substitution 2B - Metabolic syndrome - - 13061 C.1184OT Substitution p.Ser395Leu Substitution Not affected - Metabolic syndrome - PCT 13063 c.1196G>A Substitution p.Arg399His Substitution Tail - Metabolic syndrome - ■ o 13065 c.1262T>C Substitution p.Leu421Pro Substitution Tail - Metabolic syndrome - KJ " A 13067 C.1315OT Substitution p.Arg439Cys Substitution Tail - Metabolic syndrome - © 13069 C.1516OG Substitution p.His506Asp Substitution Tail - Metabolic syndrome - Ul 13047 C.1698OT Substitution P = Silent Not affected - Metabolic syndrome - © Substitte Sheet (Rule 26) Database ID cDNA Variant cDNA Variant Types Protein Variant Protein Variant Types Domain Disease Abbreviation Disease Name Omim ID Omim Syg )l 13071 c.1961_1962insG Insertion p.Thr655AsnfsX49 Frame shift Tail - Metabolic syndrome - o 12408 C.73OT Substitution p.Arg25Cys Substitution Head - Muscular dystrophy - © bU 12410 C.1130G>T Substitution p.Arg377Leu Substitution 2B - Muscular dystrophy - © 12412 C.1622G>C Substitution p.Arg541 Pro Substitution Tail - Muscular dystrophy - OC 12414 c.1045C>T Substitution p.Arg349Trp Substitution 2B - Muscular dystrophy and lipodystrophy - 17411 c.1821G>A Substitution P = Silent Not affected WRS Progeroid syndrome, neonatal 264090 % 18482 c.1940T>G Substitution p.Leu647Arg Substitution Tail WRS Progeroid syndrome, neonatal 264090 % 17009 C.1303OT Substitution p.Arg435Cys Substitution Tail RD Restrictive dermopathy 275210 # 17731 C.1303OT Substitution p.Arg435Cys Substitution Tail RD Restrictive dermopathy 275210 # 17801 C.1303OT Substitution p.Arg435Cys Substitution Tail RD Restrictive dermopathy 275210 # 9166 c.1824C>T Substitution p.[=, Val607_Gln656del] Silent, Deletion Tail RD Restrictive dermopathy 275210 # 9208 c.1968+1 G>A Substitution p.Gly567_Gln656del Deletion Tail RD Restrictive dermopathy 275210 # 17980 C.1057C>T Substitution p.Gln353X Substitution 2B - Spinal muscular atrophy with cardiac involvment - - 18424 C.868G>A Substitution p.Glu290Lys Substitution 2B SCD Sudden cardiac death 115080 # 17189 c.908_909delCT Deletion p.Ser303CysfsX26 Frame shift 2B SCD Sudden cardiac death 115080 # 17901 c.1334T>A Substitution p.Val445Glu Substitution Tail SCD Sudden cardiac death 115080 # 9022 C.1804G>A Substitution p.Gly602Ser Substitution Tail - Type A insulin resistance syndrome - - ■0 n In some embodiments the laminopathy is not Hutchinson-Gilford Progeria Syndrome (HGPS). In some embodiments, where the mutation is to LMNA, it is a LMNA mutation which does not result in an increase in the level of progerin. In some embodiments, where the mutation is to LMNA, it is not a HGPS-associated mutation. Further aspects of the present invention concern the treatment / prevention of diseases characterised by hyperlipidemia. Further aspects of the present invention concern the treatment / prevention of diseases associated with LDL receptor deficiency (i.e. a reduced level of LDL receptor protein and / or function). Hyperlipidemia refers to an elevated level of lipid or lipoprotein in the blood. Hyperlipidemia includes hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia (combination of hypertriglyceridemia and hypercholesterolemia). Hyperlipidemia is associated e.g. with atherosclerosis, hypertension and cardiovascular disease. Hypercholesterolemia is described e.g. in Bhatnagar et al., BMJ (2008) 337:a993. The UK NHS defines hypercholesterolemia as blood total cholesterol level of >5 mmol / L or blood low-density lipoprotein (LDL) level of >3 mmol / L. The US NIH defines hypercholesterolemia as blood total cholesterol level of >240 mg / dL. Hypertriglyceridemia is described e.g. in Berglund et al., J. Clin. Endocrinol. Metab. (2012) 97(9):2969-89, and is defined by blood triglyceride level >150 mg / dL (>1.7 mmol / L). In some embodiments, the disease characterised by hyperlipidemia may be a familial hyperlipidemia or an acquired (secondary) hyperlipidemia. In some embodiments a familial hyperlipidemia is selected from Buerger-Gruetz syndrome, familial apoprotein Cll deficiency, type Ic hyperlipoproteinemia, familial hypercholesterolemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia, familial hypertriglyceridemia and type V hyperlipoproteinemia. In some embodiments a familial hyperlipidemia is familial hypercholesterolemia. LDL receptor deficiency may arise e.g. as a result of mutation to LDLR. Accordingly, aspects of the present invention concern the treatment / prevention of diseases associated with mutation to LDLR. In some embodiments the mutation is known or predicted to reduce the level of one or more LDL receptor isoforms encoded by the wildtype LDLR allele and / or increase the level of one or more disease-associated LDL receptor variants. In some embodiments the disease is associated with mutation to LDLR is familial hypercholesterolemia. In some embodiments, the disease to be treated / prevented in accordance with the present invention is characterised by one or more of hyperlipidemia, hypercholesterolemia, atherosclerosis, stenosis or 91 hypertension. In some embodiments, the disease to be treated / prevented in accordance with the present invention is characterised by atherosclerosis. In some embodiments, the disease to be treated / prevented is selected from atherosclerosis, cardiovascular disease, stroke and a familial hyperlipidemia. In some embodiments, the methods comprise determining whether a subject has a disease described herein. In some embodiments the methods comprise diagnosing a disease described herein. Determining a whether a subject has a disease described herein may comprise analysing a subject for one or more symptoms / correlates of the disease. In some embodiments the subject may be suspected of having or suffering from a disease, e.g. based on the presence of other symptoms indicative of the disease in the subject or in a cell / tissue / organ of the subject. In some embodiments the subject may be considered at risk of developing the disease, e.g. because of genetic predisposition or other risk factors for the disease. In some embodiments, the methods comprise determining whether a subject has a mutation to a gene described herein. In some embodiments the methods comprise detecting a mutation to a gene described herein. Determination of mutation to a gene described herein may confirm a diagnosis or suspected diagnosis, or may confirm that the subject is at risk of developing the disease. The determination may diagnose a disease, or predisposition to a disease, for treatment / prevention with a LINC complex inhibitor. Genetic factors may be assayed by methods known to those of ordinary skill in the art, including PCR based and sequencing assays. By determining the presence of genetic factors, e.g. in a sample obtained from a subject, a diagnosis may be confirmed, and / or a subject may be classified as being at risk of developing a disease described herein, and / or a subject may be identified as being suitable for treatment with a LINC complex inhibitor. Assays may be performed in vitro on a sample obtained from a subject, or following processing of a sample obtained from a subject. The sample obtained from a subject may be of any kind. A biological sample may be taken from any tissue or bodily fluid, e.g. a blood sample, blood-derived sample, serum sample, lymph sample, semen sample, saliva sample, synovial fluid sample. A blood-derived sample may be a selected fraction of a patient’s blood, e.g. a selected cell-containing fraction or a plasma or serum fraction. A sample may comprise a tissue sample or biopsy; or cells isolated from a subject. In some embodiments, the methods comprise determining whether a subject comprises mutation to an allele of one or more of LMNA, LMNB1, LMNB2, EMD, LAP2, LBR, ZMPSTE24, SYNE-A and NUP62. In some embodiments, the methods comprise determining whether a subject comprises mutation to an allele of one or more of LMNA, LMNB1 and LMNB2. In some embodiments, the methods comprise determining whether a subject comprises mutation to an allele of LMNA. In some embodiments, the methods comprise determining whether a subject comprises mutation to an allele of LDLR. In such embodiments, detection of mutation may identify a subject as a subject to be administered a LINC complex inhibitor according to the present disclosure. Accordingly, in some embodiments the methods comprise selecting a subject determined to comprise mutation to one or more of LMNA, LMNB1, LMNB2, EMD, LAP2, LBR, ZMPSTE24, SYNE-1 and NUP62 for administration with a LINC complex inhibitor. In some embodiments the methods comprise selecting a subject determined to comprise mutation to one or more of LMNA, LMNB1 and LMNB2 for administration with a LINC complex inhibitor. In some embodiments the methods comprise selecting a subject determined to comprise mutation to LMNA for administration with a LINC complex inhibitor. In some embodiments the methods comprise selecting a subject determined to comprise mutation to LDLR for administration with a LINC complex inhibitor. In some embodiments, the methods comprise testing a sample obtained from a subject suspected of having a disease for the presence or absence of at least one LMNA mutation; wherein the presence of at least one LMNA mutation indicates that the subject is to be administered a LINC complex inhibitor according to the present disclosure. In accordance with various aspects of the present invention, a method of treating and / or preventing a disease according to the present invention may comprise one or more of the following: Increasing survival of a subject having the disease; Increasing the lifespan of a subject having the disease; Increasing cardiac function; Delaying the onset of decline of cardiac function; Increasing myocardial contractility; Increasing ejection fraction and / or fractional shortening; Reducing atherosclerosis. Subjects A subject in accordance with the present disclosure may be any animal. In some embodiments a subject may be mammalian. In some embodiments a subject may be human. In some embodiments a subject may be a non-human animal, e.g. a non-human mammal. The subject may be male orfemale. The subject may be a patient. The patient may have a disease described herein. A subject may have been diagnosed with a disease described herein, may be suspected of having a disease described herein, or may be at risk from developing a disease described herein. In embodiments according to the present invention, a subject / patient may be selected for therapy / prophylaxis according to the methods described herein based on characterisation for markers of a disease described herein. Numbered paragraphs The following numbered paragraphs (paras) provide further statements of features and combinations of features which are contemplated in connection with the present invention. In accordance with some of the various aspects and embodiments of the present invention, subjectmatter according to the following numbered paras may be specifically disclaimed. 1. An isolated nucleic acid molecule, wherein the nucleic acid molecule comprises an expression vector and a transgene, whereby the transgene is operably linked to the expression vector, wherein expression of the transgene in a transfected cell results in disruption of a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex in the transfected cell. 2. The nucleic acid molecule of para 1, wherein the expression vector is a cardiac- or card io myocytespecific expression vector. 3. The nucleic acid molecule of para 1 or para 2, wherein the expression vector comprises a cardiac-or cardiomyocyte-specific promoter. 4. The nucleic acid molecule of para 3, wherein the expression vector comprises a cardiac- or cardiomyocyte-specific promoter selected from the group comprising a cardiac troponin T promoter (cTnT), a a-myosin heavy chain (a-MHC) promoter and a myosin light chain (MLC2v) promoter. 5. The nucleic acid molecule of para 3 or 4, wherein the cardiomyocyte-specific promoter is chicken cardiac troponin T (cTnT) promoter. 6. The nucleic acid molecule of any one of the preceding paras, wherein the expression vector is a virus expression vector. 7. The nucleic acid molecule of para 6, wherein the virus expression vector is selected from the group comprising Lentivirus, Adenovirus and Adeno-associated virus (AAV). 8. The nucleic acid molecule of any one of the preceding paras, wherein the adeno-associated virus expression vector (AAV) has cardiac tropism / is cardiotropic. 9. The nucleic acid molecule of any one of the preceding paras, wherein in the AAV vector is selected from the group consisting of AAV9 (serotype 9), AAV1 (serotype 1), AAV6 (serotype 6), AAV8 (serotype 8), AAV2i8, and AAV9.45. 10. The nucleic acid molecule of any one of the preceding paras, wherein in the AAV vector is AAV9 (serotype 9). 11. The nucleic acid molecule of any one of the preceding paras, wherein transgene comprises nucleic acid sequences for expressing a lumenal domain of a SUN domain-containing protein, an N-terminal signal sequence, a signal peptidase cleavage site, and a C-terminal targeting peptide sequence. 12. The nucleic acid molecule of para 11, wherein the lumenal domain of the SUN domain-containing protein comprises a coiled coil domain and a SUN domain. 13. The nucleic acid molecule of para 11, wherein the coiled coil domain is upstream of the SUN domain. 14. The nucleic acid molecule of any one of the preceding paras, wherein the transgene further comprises nucleic acid sequences for expressing an N-terminal signal sequence, a signal peptidase cleavage site, and a C-terminal targeting peptide sequence. 15. The nucleic acid molecule of any one of the preceding paras, wherein the transgene comprises nucleic acid sequences for expressing an N-terminal signal sequence, a signal peptidase cleavage site, and a C-terminal targeting peptide sequence, and either the lumenal domain of the SUN domaincontaining protein or the SUN domain. 16. The nucleic acid molecule of any one of paras 11 to 15, wherein the SUN domain protein is SUN1 orSUN2. 17. The nucleic acid molecule of any one of paras 11 to 16, wherein the N-terminal signal sequence is derived from a secretory protein or a Type I transmembrane protein. 18. The nucleic acid molecule of para 17, wherein the secretory protein or Type I transmembrane protein is selected from the group consisting of human serum albumin, proinsulin, transferrin receptor, EGF receptor, pre-pro-opiomelanocortin, pancreatic digestive enzymes (for example, proteases, amylases and lipases), endoplasmic reticulum lumenal proteins, for example protein disulphide isomerases, GRP94 and combinations thereof. 19. The nucleic acid molecule of para 18, wherein the N-terminal signal sequence is derived from human serum albumin. 20. The nucleic acid molecule of any one of paras 11 to 19, wherein the N-terminal signal sequence is not preceded at its N-terminus by any other tags. 21. The nucleic acid molecule of any one of paras 11 to 20, wherein the signal peptidase cleavage site is a signal peptidase cleavage site derived from or is one of the group consisting of human serum albumin, proinsulin, transferrin receptor, EGF receptor, pre-pro-opiomelanocortin, carboxypeptidases, complement proteins, fibrinogen, cytokines, chemokines, fibrinogen, pancreatic digestive enzymes (for example, proteases, amylases and lipases), endoplasmic reticulum lumenal proteins, such as protein disulphide isomerases, GRP94 and combinations thereof. 22. The nucleic acid molecule of para 21, wherein the signal peptidase cleavage site is a signal peptidase cleavage site derived from human serum albumin. 23. The nucleic acid molecule of any one of paras 11 to 22, wherein the C-terminal targeting peptide sequence prevents secretion of a peptide expressed from the transgene according to any one of paras 1 to 19. 24. The nucleic acid molecule of any one of paras 11 to 23, wherein the C-terminal targeting peptide sequence is a KDEL sequence. 25. The nucleic acid molecule of any one of paras 1 to 24, wherein the transgene further comprises an epitope tag. 26. The nucleic acid molecule of para 25, wherein the optional epitope tag is N-terminal, or located anywhere in the nucleic acid molecule except downstream of (after) the C-terminal targeting peptide sequence [for example KDEL], or located anywhere in the nucleic acid molecule except upstream of (before) the N-terminal signal sequence. 27. The nucleic acid molecule of para 26, wherein the optional epitope tag is selected from the group consisting of cellulose binding domain (CBD), chloramphenicol acetyl transferase (CAT), dihydrofolate reductase (DHFR), one or more FLAG tags, glutathione S-transferase (GST), green fluorescent protein (GFP), haemagglutinin A (HA), histidine (His), Herpes simplex virus (HSV), luciferase, maltose-binding protein (MBP), c-Myc, Protein A, Protein G, streptavidin, T7, thioredoxin, V5, vesicular stomatitis virus glycoprotein (VSV-G), and combinations thereof. 28. The nucleic acid molecule of para 27, wherein the epitope tag is haemagglutinin A (HA). 29. The nucleic acid molecule of any one of the preceding paras, wherein the vector is the adeno-associated virus vector (AAV) comprising the chicken cardiac troponin T promoter (cTnT), and the transgene according to any one of paras 1 to 28, wherein the lumenal domain of the SUN domaincontaining protein is derived from SUN1, wherein the N-terminal signal sequence and the signal peptidase cleavage site are each derived from human serum albumin, wherein the C-terminal targeting peptide sequence is the KDEL sequence, and wherein the transgene further comprises haemagglutinin (HA) as the N-terminal epitope tag; optionally wherein the vector comprises the nucleic acid sequence shown in SEQ ID NO:3 (see e.g. Figure 10). 30. The nucleic acid molecule of any one of the preceding paras, wherein the vector is the adeno-associated virus vector (AAV) comprising the chicken cardiac troponin T promoter (cTnT), and the transgene according to any one of paras 1 to 28, wherein the lumenal domain of the SUN domaincontaining protein is derived from SUN2, wherein the an N-terminal signal sequence and the signal peptidase cleavage site are each derived from human serum albumin, and wherein the C-terminal targeting peptide sequence is the KDEL sequence, and wherein the transgene further comprises haemagglutinin (HA) as the N-terminal epitope tag; optionally wherein the vector comprises the nucleic acid sequence shown in SEQ ID NO:5 (see e.g. Figure 10). 31. The nucleic acid molecule of any one of paras 1 to 10, wherein the transgene comprises nucleic acid sequences for expressing a KASH domain, and an N-terminal stabiliser polypeptide sequence. 32. The nucleic acid molecule of para 31, wherein the KASH domain comprises a transmembrane domain and a SUN-interacting peptide. 33. The nucleic acid molecule of any one of paras 31 to 32, wherein the KASH domain is selected from the group consisting of KASH1 (derived from Nesprin-1 (SYNE1 gene)), KASH2 (derived from Nesprin-2 (SYNE2 gene)), KASH3 (derived from Nesprin-3 (SYNE3 gene)), KASH4 (derived from Nesprin-4 (SYNE4 gene)), and KASH5 (derived from KASH5 / CCDC155 (KASH5 gene)). 34. The nucleic acid molecule of any one of paras 1 to 10, wherein the transgene comprises nucleic acid sequences for expressing a CRISPR-Cas or other synthetic nuclease system to modify nucleic acid that encodes the SUN domain or KASH domain of endogenous Sun or Nesprin protein, respectively. 35. The nucleic acid molecule of para 34, wherein the transgene comprises nucleic acid sequences for expressing a CRISPR-Cas. 36. The nucleic acid molecule of any one of paras 1 to 33, wherein the transgene is a dominant negative construct. 37. The nucleic acid molecule of any one of the preceding paras, wherein the transgene is a humanised or human transgene. 38. The nucleic acid molecule of any one of the preceding paras, wherein expression of the transgene results in the disruption of the protein-protein interaction between SUN and KASH of the LINC complex. 39. The nucleic acid molecule of para 38, wherein the disruption of the protein-protein interaction between SUN and KASH of the LINC complex occurs between the protein interactions selected from the group consisting of Sun1+Nesprin-1, Sun2+Nesprin-1, Sun1+Nesprin-2, Sun1+Nesprin-3, Sun2+Nesprin-2, and Sun2+Nesprin-3. 40. The nucleic acid molecule of para 39, wherein the disruption of the protein-protein interaction between SUN and KASH of the LINC complex occurs between Sun1 and Nesprin-1. 41. The nucleic acid molecule of any one of the preceding paras, wherein the AAV vector is formulated for delivery into the myocardium of a subject. 42. The nucleic acid molecule of any one of the preceding paras for use in treating a disease caused by one or more Lmna mutations in a subject. 43. The nucleic acid molecule of para 42, wherein the disease is selected from the group consisting of restrictive dermopathy, familial partial lipodystrophy (for example, Dunnigan type), mandibuloacral dysplasia with type A lipodystrophy, metabolic syndrome, Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease type 2B1 and diseases presented in normal font in Table 1. 44. The nucleic acid molecule of any one of the preceding paras for use in treating cardiovascular disease in a subject. 45. The nucleic acid molecule of para 42 or 43, wherein the disease or the cardiovascular disease is characterised by the presence of at least one Lmna mutation. 46. The nucleic acid molecule of any one of paras 44 to 45, wherein the cardiovascular disease is selected from the group consisting of laminopathy, cardiomyopathy, such as dilated cardiomyopathy 98 (DCM), dilated cardiomyopathy 1A, dilated cardiomyopathy with conduction system defects, cardiomyopathy with advanced AV block and arrhythmia, lone atrial fibrillation; muscular dystrophy (often associated with cardiomyopathy), such as cardiomyopathy associated with Emery-Dreifuss muscular dystrophy (autosomal dominant), cardiomyopathy associated with Emery-Dreifuss muscular dystrophy (autosomal recessive), cardiomyopathy associated with Limb-girdle muscular dystrophy type 1B, cardiomyopathy associated with congenital muscular dystrophy; premature aging syndromes (thought to be primarily vascular, but may have cardiac involvement) such as cardiomyopathy associated with Atypical Werner syndrome, cardiomyopathy associated with Hutchinson-Gilford progeria syndrome and the like, as well as diseases presented in bold font in Table 1. 47. An adeno-associated virus vector (AAV) comprising the cardiac troponin T promoter (cTnT), and the transgene according to any one of paras 11 to 30 or paras 34 to 38. 48. A pharmaceutical composition comprising the nucleic acid molecule according to any one of paras 1 to 41. 49. A method of treating a disease in a subject, the method comprising administration of a pharmaceutically effective amount of the nucleic acid molecule according to any one of paras 1 to 41, or the pharmaceutical composition of para 48. 50. The method of para 49, wherein the disease is characterised by the presence of at least one Lmna mutation. 51. The method of any one of paras 49 to 50, wherein the Lmna mutation(s) affect(s) lamin A isoform, or lamin C isoform of the Lmna gene, or both lamin A / C isoforms. 52. The method of any one of paras 49 to 51, wherein the disease is selected from the group consisting of restrictive dermopathy, familial partial lipodystrophy (for example, Dunnigan type), mandibuloacral dysplasia with type A lipodystrophy, metabolic syndrome, Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease type 2B1 and diseases present in normal font in Table 1. 53. The method according to any one of paras 49 to 51, wherein the disease is a cardiovascular disease selected from the group consisting of laminopathy, cardiomyopathy, such as dilated cardiomyopathy (DCM), dilated cardiomyopathy 1A, dilated cardiomyopathy with conduction system defects, cardiomyopathy with advanced AV block and arrhythmia, lone atrial fibrillation; muscular dystrophy (often associated with cardiomyopathy), such as cardiomyopathy associated with Emery-Dreifuss muscular dystrophy (autosomal dominant), cardiomyopathy associated with Emery-Dreifuss muscular dystrophy (autosomal recessive), cardiomyopathy associated with Limb-girdle muscular dystrophy type 1B, cardiomyopathy associated with congenital muscular dystrophy; premature aging syndromes (thought to be primarily vascular, but may have cardiac involvement) such as cardiomyopathy associated with Atypical Werner syndrome, cardiomyopathy associated with Hutchinson-Gilford progeria syndrome; and diseases presented in bold font in Table 1. 54. The method of any one of paras 49 to 53, wherein the subject is a non-human mammal or a human; optionally wherein the non-human mammal is a mouse; optionally wherein the mouse is an N195K mouse (LmnaN 195K / N195K), ora Lmna conditional knockout (LmnafloMox). 55. Use of the pharmaceutical composition according to para 48 or the nucleic acid molecule according to any one of paras 1 to 41 in the manufacture of a medicament for treating a disease caused by one or more Lmna mutations or cardiovascular disease. 56. The use of para 55, wherein the disease is selected from the group consisting of restrictive dermopathy, familial partial lipodystrophy (for example, Dunnigan type), mandibuloacral dysplasia with type A lipodystrophy, metabolic syndrome, Charcot-Marie-Tooth disease type 2, Charcot-Marie-Tooth disease type 2B1 and diseases presented in normal font in Table 1. 57. The use of para 55, wherein the cardiovascular disease is selected from the group consisting of laminopathy, cardiomyopathy, such as dilated cardiomyopathy (DCM), dilated cardiomyopathy 1A, dilated cardiomyopathy with conduction system defects, cardiomyopathy with advanced AV block and arrhythmia, lone atrial fibrillation; muscular dystrophy (often associated with cardiomyopathy), such as cardiomyopathy associated with Emery-Dreifuss muscular dystrophy (autosomal dominant), cardiomyopathy associated with Emery-Dreifuss muscular dystrophy (autosomal recessive), cardiomyopathy associated with Limb-girdle muscular dystrophy type 1B, cardiomyopathy associated with congenital muscular dystrophy; premature aging syndromes (thought to be primarily vascular, but may have cardiac involvement) such as cardiomyopathy associated with Atypical Werner syndrome, cardiomyopathy associated with Hutchinson-Gilford progeria syndrome and the like, as well as diseases presented in bold font in Table 1. 58. The pharmaceutical composition according to para 48 for use in therapy. 59. A method of screening fordrug candidates capable of inhibiting the interaction of the proteins of a LINO complex in a cell, which comprises: (a) combining the proteins of said LINO complex in the presence of a drug to form a first complex; (b) combining the proteins in the absence of said drug to form a second complex; (c) measuring the amount of said first complex and said second complex; and (d) comparing the amount of said first complex with the amount of said second complex, 100 wherein if the amount of said first complex is less than the amount of said second complex, then the drug is a drug candidate for inhibiting the interaction of the proteins of said LINC complex in a cell. 60. The method of para 59, wherein the drug candidate disrupts the protein-protein interaction between SUN and KASH of the LINC complex. 61. The method of para 60, wherein the drug candidate disrupts the interaction between Sun1 and Nesprin-1 proteins. 62. The method of any one of paras 59 to 61, wherein the screening is an in vitro screening. 63. The method of any one of paras 59 to 62, wherein the complex is measured by an ELISA method or by a fluorescence anisotropy method. 64. The method of any one of paras 59 to 63, wherein if the amount of said first complex is less than the amount of said second complex, then said drug is a drug candidate for inhibiting the interaction of said proteins. 65. The method of any one of paras 59 to 64, wherein recombinant SUN and KASH domains are used. 65. The method of any one of paras 59 to 65, wherein recombinant SUN and KASH domains are used; optionally wherein recombinant SUN domain is immobilized on a solid surface and recombinant KASH domain is labelled with an enzyme that can generate a colorimetric or chemiluminescent readout (compounds that fail to inhibit the SUN-KASH interaction will result in a well in the plate where the recombinant SUN would bind to the enzyme-linked KASH domain. Following wash steps and incubation with colorimetric or chemiluminescent enzyme substrates, the presence of the SUN-KASH interaction can be detected in standard plate readers. If the compound can inhibit SUN-KASH interaction, then following the wash step, the KASH domain would be removed, and there would be reduced or no enzymatic reaction in the well). optionally wherein the KASH domain is fluorescently labelled with a fluorescein moiety and fluorescence anisotropy of the KASH domain interacting with SUN domain may be measured using standard equipment such as a plate reader incorporating a fluorescence spectrometer function; optionally wherein if the amount of said first complex is less than the amount of said second complex there will be a difference in the fluorescence anisotropy of the fluorescent KASH and said drug is a drug candidate for inhibiting the interaction of said proteins. Sequence identity Pairwise and multiple sequence alignment for the purposes of determining percent identity between two or more amino acid or nucleic acid sequences can be achieved in various ways known to a person of skill in the art, for instance, using publicly available computer software such as 5 ClustalOmega (Sbding, J. 2005, Bioinformatics 21,951-960), T-coffee (Notredame et al. 2000, J. Mol. Biol. (2000) 302, 205-217), Kalign (Lassmann and Sonnhammer2005, BMC Bioinformatics, 6(298)) and MAFFT (Katoh and Standley 2013, Molecular Biology and Evolution, 30(4) 772-780 software). When using such software, the default parameters, e.g. for gap penalty and extension penalty, are preferably used. 10 Sequences SEQ ID NO: DESCRIPTION SEQUENCE 1 pAdDeltaF6 TCGACGGTATCGATAAGCTTGATATCGAATTCCTGCAGCCCGGGGGATCCACTAGTTCTAGAG CGGCCGCCACCGCGGTGGAGCTCCAGC Illi GTTCCCTTTAGTGAGGGTTAATTTCGAGCTTG GCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATTCCACACAACAT ACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAACTCACATTAATT GCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATC GGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCCTCGCTCACTGA CTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATAC GGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGG CCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGC ATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGG CGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACC TGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAG TTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACC GCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACT GGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTT GAAGTGGTGGCCTAACTACGGCTACACTAGAAGGACAGTATTTGGTATCTGCGCTCTGCTGAA GCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAG CGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCT TTGATC I I I I (J I ACGGGG I (J I GACGC I (JAG I GGAA(JGAAAA(J I (JA(JG I IAAGGGA Illi GGTCA TGAGATTATCAAAAAGGATCTTCACCTAGATCC Illi AAA I IAAAAAI GAAG Illi AAATCAATCT AAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAGGCACCTATCTCA GCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGATAACTACGATAC GGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCACGCTCACCGGCT CCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTGGTCCTGCAACT TTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTAGTTCGCCAGTTA ATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTCGTCGTTTGGTAT GGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGCAAA AAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCAC TCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGATGC Illi CTGTG ACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGAGTTGCTCTTGCC CGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAA ACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGTTCGATGTAACCC ACTCGTGCACCCAACTGATCTTCAGCATC Illi ACTTTCACCAGCGTTTCTGGGTGAGCAAAAA CAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTGAATACTCATAC TCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGGATACATATTTG AATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGA CGTCTAAGAAACCATTATTATCATGACATTAACCTATAAAAATAGGCGTATCACGAGGCCCTTTC GTCTTCAAGAATTCTCATGTTTGACAGCTTATCATCGATAAGCTTTAATGCGGTAGTTTATCACA GTTAAATTGCTAACGCAGTCAGGCACCGTGTATGAAATCTAACAATGCGCTCATCGTCATCCTC GGCACCGTCACCCTGGATGCTGTAGGCATAGGCTTGGTTATGCCGGTACTGCCGGGCCTCTTG CGGGATATCGTCCATTCCGACAGCATCGCCAGTCACTATGGCGTGCTGCTAGCGCTATATGCG TTGATGCAATTTCTATGCGCACCCGTTCTCGGAGCACTGTCCGACCGCTTTGGCCGCCGCCCA GTCCTGCTCGCTTCGCTACTTGGAGCCACTATCGACTACGCGATCATGGCGACCACACCCGTC CTGTGGATCCGGCGCACACCAAAAACGTCAC Illi GCCACATCCGTCGCTTACATGTGTTCCGC CACACTTGCAACATCACACTTCCGCCACACTACTACGTCACCCGCCCCGTTCCCACGCCCCGC GCCACGTCACAAACTCCACCCCCTCATTATCATATTGGCTTCAATCCAAAATAAATCATCAATAA TATACCTTA Illi GGATTGAAGCCAATATGATAATGAGGGGGTGGAGTTTGTGACGTGGCGCGG GGCGTGGGAACGGGGCGGGTGACGTAGG Illi AGGGCGGAGTAACTTGTATGTGTTGGGAAT TGTAG Illi CTTAAAATGGGAAGTTACGTAACGTGGGAAAACGGAAGTGACGATTTGAGGAAGT TGTGGG I I I I I I GGC I I I UG I I I (J I GGGCG I AGG I I CGCG I GCGG I I I I (J I GGG I G I I I I I I GT GGACTTTAACCGTTACGTCAI I I I I I AG I UUIAIAIAI AC I CGC I (J I GCAC I I GGCCC I I I I I I AC ACTGTGACTGATTGAGCTGGTGCCGTGTCGAGTGGTGI I I I I I IAAI AGG I I I ICI I I I I IACTG GTAAGGCTGACTGTTAGGCTGCCGCTGTGAAGCGCTGTATGTTGTTCTGGAGCGGGAGGGTG CTA Illi GCC I AGGCAGGAGGG I I I I I CAGG I G I I IA I G I G I I I I I UI U I CO I AI I AA I I I I GTTA TACCTCCTATGGGGGCTGTAATGTTGTCTCTACGCCTGCGGGTATGTATTCCCCCGGGCTATTT CGGTCGCTTTTTAGCACTGACCGATGAATCAACCTGATGTGTTTACCGAGTCTTACATTATGACT CCGGACATGACCGAGGAGCTGTCGGTGGTGCI I I I I AA I CACGGIGACCAGI I I I I I IACGGTC ACGCCGGCATGGCCGTAGTCCGTCTTATGCTTATAAGGGTTGTTTTTCCTGTTGTAAGACAGGC TTCTAATGTTTAAATG I I I I I I I G I IAI I I IAI I I I GTGTTTATGCAGAAACCCGCAGACATGTTTG AGAGAAAAATGGTGTCTTTTTCTGTGGTGGTTCCGGAGCTTACCTGCCTTTATCTGCATGAGCA TGACTACGATGTGCTTTC I I I I I I GCGCGAGGCI I I GCC I GA I I I I I I GAGCAGCACCTTGCATT TTATATCGCCGCCCATGCAACAAAGCTTACATCGGGGCTACGCTGGTTAGCATAGCTCCGAGT ATGCGTGTCATAATCAGTGTGGGTTC Illi GTCAAGGTTCCTGGCGGGGAAGTGGCCGCGCTG GTCCGTGCAGACCTGCACGATTATGTTCAGCTGGCCCTGCGAAGGGACCTACGGGATCGCGG TAI I I I IGI I AA I G I I CCGC I I I I GAA I U I IA IACAGG I UI G I GAGGAACC I GAAI I I I I GCAATC ATGATTCGCTGCTTGAGGCTGAAGGTGGAGGGCGCTCTGGAGCAGATTTTTACAATGGCCGGA CTTAATATTCGGGATTTGCTTAGAGATATATTGAGAAGGTGGCGAGATGAGAATTATTTGGGCA TGGTTGAAGGTGCTGGAATGTTTATAGAGGAGATTCACCCTGAAGGGTTTAGCCTTTACGTCCA CTTGGACGTGAGGGCCGTTTGCC Illi GGAAGCCATTGTGCAACATCTTACAAATGCCATTATC TGTTCTTTGGCTGTAGAGTTTGACCACGCCACCGGAGGGGAGCGCGTTCACTTAATAGATCTTC AI I I I GAGG Illi GGAIAAI U I I I I GGAATAAAAAAAAAAACATGGTTCTTCCAGCTCTTCCCGC TCCTCCCGTGTGTGACTCGCAGAACGAATGTGTAGGTTGGCTGGGTGTGGCTTATTCTGCGGT GGTGGATGTTATCAGGGCAGCGGCGCATGAAGGAGTTTACATAGAACCCGAAGCCAGGGGGC GCCTGGATGCTTTGAGAGAGTGGATATACTACAACTACTACACAGAGCGATCTAAGCGGCGAG ACCGGAGACGCAGATCTGTTTGTCACGCCCGCACCTGG Illi GCTTCAGGAAATATGACTACGT CCGGCGTTCCATTTGGCATGACACTACGACCAACACGATCTCGGTTGTCTCGGCGCACTCCGT ACAGTAGGGATCGTCTACCTCC Illi GAGACAGAAACCCGCGCTACCATACTGGAGGATCATC CGCTGCTGCCCGAATGTAACACTTTGACAATGCACAACGTGAGTTACGTGCGAGGTCTTCCCT GCAGTGTGGGATTTACGCTGATTCAGGAATGGGTTGTTCCCTGGGATATGGTTCTAACGCGGG AGGAGCTTGTAATCCTGAGGAAGTGTATGCACGTGTGCCTGTGTTGTGCCAACATTGATATCAT GACGAGCATGATGATCCATGGTTACGAGTCCTGGGCTCTCCACTGTCATTGTTCCAGTCCCGG TTCCCTGCAGTGTATAGCCGGCGGGCAGG Illi GGCCAGCTGGTTTAGGATGGTGGTGGATG GCGCCATGTTTAATCAGAGGTTTATATGGTACCGGGAGGTGGTGAATTACAACATGCCAAAAGA GGTAATGTTTATGTCCAGCGTGTTTATGAGGGGTCGCCACTTAATCTACCTGCGCTTGTGGTAT GATGGCCACGTGGGTTCTGTGGTCCCCGCCATGAGCTTTGGATACAGCGCCTTGCACTGTGG GA I I I I GAACAATATTGTGGTGCTGTGCTGCAGTTACTGTGCTGATTTAAGTGAGATCAGGGTG CGCTGCTGTGCCCGGAGGACAAGGCGCCTTATGCTGCGGGCGGTGCGAATCATCGCTGAGGA GACCACTGCCATGTTGTATTCCTGCAGGACGGAGCGGCGGCGGCAGCAGTTTATTCGCGCGC TGCTGCAGCACCACCGCCCTATCCTGATGCACGATTATGACTCTACCCCCATGTAGGCGTGGA CTTCTCCTTCGCCGCCCGTTAAGCAACCGCAAGTTGGACAGCAGCCTGTGGCTCAGCAGCTGG ACAGCGACATGAACTTAAGTGAGCTGCCCGGGGAGTTTATTAATATCACTGATGAGCGTTTGGC TCGACAGGAAACCGTGTGGAATATAACACCTAAGAATATGTCTGTTACCCATGATATGATGCTTT TTAAGGCCAGCCGGGGAGAAAGGACTGTGTACTCTGTGTGTTGGGAGGGAGGTGGCAGGTTG AATACTAGGGTTCTGTGAGTTTGATTAAGGTACGGTGATCTGTATAAGCTATGTGGTGGTGGGG CTATACTACTGAATGAAAAATGACTTGAAA Illi CTGCAATTGAAAAATAAACACGTTGAAACATA ACACAAACGATTCTTTATTCTTGGGCAATGTATGAAAAAGTGTAAGAGGATGTGGCAAATATTTC ATTAATGTAGTTGTGGCCAGACCAGTCCCATGAAAATGACATAGAGTATGCACTTGGAGTTGTG TCTCCTGTTTCCTGTGTACCGTTTAGTGTAATGGTTAGTGTTACAGGTTTAG Illi GTCTCCGTT TAAGTAAACTTGACTGACAATGTTAC Illi GGCAG Illi ACCG I GAGA Illi GGATAAGCTGATA GGTTAGGCATAAATCCAACAGCGTTTGTATAGGCTGTGCCTTCAGTAAGATCTCCATTTCTAAA GTTCCAATATTCTGGGTCCAGGAAGGAATTGTTTAGTAGCACTCCA Illi CGTCAAATCTTATAA TAAGATGAGCACTTTGAACTGTTCCAGATATTGGAGCCAAACTGCCTTTAACAGCCAAAACTGA AACTGTAGCAAGTATTTGACTGCCACA Illi GTTAAGACCAAAGTGAGTTTAGCATCTTTCTCTG CATTTAGTCTACAGTTAGGAGATGGAGCTGGTGTGGTCCACAAAGTTAGCTTATCATTATTTTTG TTTCCTACTGTAATGGCACCTGTGCTGTCAAAACTAAGGCCAGTTCCTAGTTTAGGAACCATAG CCTTGTTTGAATCAAATTCTAGGCCATGGCCAAI I I I I G I I I IGAGGGGATTTGTGTTTGGTGCA TTAGGTGAACCAAATTCAAGCCCATCTCCTGCATTAATGGCTATGGCTGTAGCGTCAAACATCA ACCCCTTGGCAGTGCTTAGGTTAACCTCAAGCTTTTTGGAATTGTTTGAAGCTGTAAACAAGTAA AGGCCTTTGTTGTAGTTAATATCCAAGTTGTGGGCTGAGTTTATAAAAAGAGGGCCCTGTCCTA GTCTTAGATTTAGTTGG Illi GAGCATCAAACGGATAACTAACATCAAGTATAAGGCGTCTGTTT TGAGAATCAATCCTTAGTCCTCCTGCTACATTAAGTTGCATATTGCCTTGTGAATCAAAACCCAA GGCTCCAGTAACTTTAGTTTGCAAGGAAGTATTATTAATAGTCACACCTGGACCAGTTGCTACG GTCAAAGTGTTTAGGTCGTCTGTTACATGCAAAGGAGCCCCGTACTTTAGTCCTAG Illi CCA I I TTGTGTATAAATGGGCTCTTTCAAGTCAATGCCCAAGCTACCAGTGGCAGTAGTTAGAGGGGGT GAGGCAGTGATAGTAAGGGTACTGCTATCGGTGGTGGTGAGGGGGCCTGATGTTTGCAGGGC TAGCTTTCCTTCTGACACTGTGAGGGGTCCTTGGGTGGCAATGCTAAGTTTGGAGTCGTGCAC GGTTAGCGGGGCCTGTGATTGCATGGTGAGTGTGTTGCCCGCGACCATTAGAGGTGCGGCGG CAGCCACAGTTAGGGCTTCTGAGGTAACTGTGAGGGGTGCAGATATTTCCAGGTTTATGTTTGA CTTGG I I I I I I I GAGAGG I GGGC I CACAG I GG I IACA Illi GGGAGGTAAGGTTGCCGGCCTC GTCCAGAGAGAGGCCGTTGCCCA Illi GAGCGCAAGCATGCCATTGGAGGTAACTAGAGGTTC GGATAGGCGCAAAGAGAGTACCCCAGGGGGACTCTCTTGAAACCCATTGGGGGATACAAAGG GAGGAGTAAGAAAAGGCACAGTTGGAGGACCGGTTTCCGTGTCATATGGATACACGGGGTTGA AGGTATCTTCAGACGGTCTTGCGCGCTTCATCTGCAACAACATGAAGATAGTGGGTGCGGATG GACAGGAACAGGAGGAAACTGACATTCCATTTAGATTGTGGAGAAAGTTTGCAGCCAGGAGGA AGCTGCAATACCAGAGCTGGGAGGAGGGCAAGGAGGTGCTGCTGAATAAACTGGACAGAAATT TGCTAACTGA Illi AAG IAAG I GA I GCI I IAI IAI I I I I I I I IATTAGTTAAAGGGAATAAGATCC CCGGGTACTCTAGTTAATTAACTAGAGGATCTTGATGTAATCCAAGGTTAGGACAGTTGCAAAT CACAGTGAGAACACAGGGTCCCCTGTCCCGCTCAACTAGCAGGGGGCGCTGGGTAAACTCCC GAATCAGGCTACGGGCAAGCTCTCCCTGGGCGGTAAGCCGGACGCCGTGCGCCGGGCCCTC GATATGATCCTCGGGCAATTCAAAGTAGCAAAACTCACCGGAGTCGCGGGCAAAGCACTTGTG GCGGCGACAGTGGACCAGGTGTTTCAGGCGCAGTTGCTCTGCCTCTCCACTTAACATTCAGTC GTAGCCGTCCGCCGAGTCCTTTACCGCGTCAAAGTTAGGAATAAATTGATCCGGATAGTGGCC GGGAGGTCCCGAGAAGGGGTTAAAGTAGACCGATGGCACAAACTCCTCAATAAATTGCAGAGT TCCAATGCCTCCAGAGCGCGGCTCAGAGGACGAGGTCTGCAGAGTTAGGATTGCCTGACGAG GCGTGAATGAAGGACGGCCGGCGCCGCCGATCTGAAATGTCCCGTCCGGACGGAGACCAAGC GAGGAGCTCACCGACTCGTCGTTGAGCTGAATACCTCGCCCTCTGATTGTCAGGTGAGTTATA CCCTGCCCGGGCGACCGCACCCTGTGACGAAAGCCGCCCGCAAGCTGCGCCCCTGAGTTAGT CATCTGAACTTCGGCCTGGGCGTCTCTGGGAAGTACCACAGTGGTGGGAGCGGGACTTTCCT GGTACACCAGGGCAGCGGGCCAACTACGGGGATTAAGGTTATTACGAGGTGTGGTGGTAATA GCCGCCTGTTCCAAGAGAATTCGGTTTCGGTGGGCGCGGATTCCGTTGACCCGGGATATCATG TGGGGTCCCGCGCTCATGTAGTTTATTCGGGTTGAGTAGTCTTGGGCAGCTCCAGCCGCAAGT CCCATTTGTGGCTGGTAACTCCACATGTAGGGCGTGGGAATTTCCTTGCTCATAATGGCGCTGA CGACAGGTGCTGGCGCCGGGTGTGGCCGCTGGAGATGACGTAG Illi CGCGCTTAAATTTGA GAAAGGGCGCGAAACTAGTCCTTAAGAGTCAGCGCGCAGTATTTACTGAAGAGAGCCTCCGCG TCTTCCAGCGTGCGCCGAAGCTGATCTTCGCI I I I GTGATACAGGCAGCTGCGGGTGAGGGAT CGCAGAGACCTG I I I I I IAI I I I CAGCTCTTGTTCTTGGCCCCTGCTCTGTTGAAATATAGCATA CAGAGTGGGAAAAATCCTGTTTCTAAGCTCGCGGGTCGATACGGGTTCGTTGGGCGCCAGACG CAGCGCTCCTCCTCCTGCTGCTGCCGCCGCTGTGGATTTCTTGGGCTTTGTCAGAGTCTTGCT ATCCGGTCGCCTTTGCTTCTGTGTGGCCGCTGCTGTTGCTGCCGCTGCCGCTGCCGCCGGTG CAGTATGGGCTGTAGAGATGACGGTAGTAATGCAGGATGTTACGGGGGAAGGCCACGCCGTG ATGGTAGAGAAGAAAGCGGCGGGCGAAGGAGATGTTGCCCCCACAGTCTTGCAAGCAAGCAA CTATGGCGTTCTTGTGCCCGCGCCATGAGCGGTAGCCTTGGCGCTGTTGTTGCTCTTGGGCTA ACGGCGGCGGCTGCTTGGACTTACCGGCCCTGGTTCCAGTGGTGTCCCATCTACGGTTGGGT CGGCGAACGGGCAGTGCCGGCGGCGCCTGAGGAGCGGAGGTTGTAGCCATGCTGGAACCGG TTGCCGATTTCTGGGGCGCCGGCGAGGGGAATGCGACCGAGGGTGACGGTGTTTCGTCTGAC ACCTCTTCGACCTCGGAAGCTTCCTCGTCTAGGCTCTCCCAGTCTTCCATCATGTCCTCCTCCT CCTCGTCCAAAACCTCCTCTGCCTGACTGTCCCAGTATTCCTCCTCGTCCGTGGGTGGCGGCG GCAGCTGCAGCTTCTTTTTGGGTGCCATCCTGGGAAGCAAGGGCCCGCGGCTGCTGCTGATA GGGCTGCGGCGGCGGGGGGATTGGGTTGAGCTCCTCGCCGGACTGGGGGTCCAAGTAAACC CCCCGTCCCTTTCGTAGCAGAAACTCTTGGCGGGCTTTGTTGATGGCTTGCAATTGGCCAAGA ATGTGGCCCTGGGTAATGACGCAGGCGGTAAGCTCCGCATTTGGCGGGCGGGATTGGTCTTC GTAGAACCTAATCTCGTGGGCGTGGTAGTCCTCAGGTACAAATTTGCGAAGGTAAGCCGACGT CCACAGCCCCGGAGTGAGTTTCAACCCCGGAGCCGCGGAC Illi CGTCAGGCGAGGGACCCT GCAGCTCAAAGGTACCGATAATTTGACTTTCGTTAAGCAGCTGCGAATTGCAAACCAGGGAGC GGTGCGGGGTGCATAGGTTGCAGCGACAGTGACACTCCAGTAGACCGTCACCGCTCACGTCT TCCATTATGTCAGAGTGGTAGGCAAGGTAGTTGGCTAGCTGCAGAAGGTAGCAGTGGCCCCAA AGCGGCGGAGGGCATTCGCGGTACTTAATGGGCACAAAGTCGCTAGGAAGTGCACAGCAGGT GGCGGGCAAGATTCCTGAGCGCTCTAGGATAAAGTTCCTAAAGTTCTGCAACATGCTTTGACTG GTGAAGTCTGGCAGACCCTGTTGCAGGG Illi AAGCAGGCGTTCGGGGAAAATGATGTCCGCC AGGTGCGCGGCCACGGAGCGCTCGTTGAAGGCCGTCCATAGGTCCTTCAAG Illi GCTTTAGC AGTTTCTGCAGCTCCTTGAGGTTGCACTCCTCCAAGCACTGCTGCCAAACGCCCATGGCCGTC TGCCAGGTGTAGCATAGAAATAAGTAAACGCAGTCGCGGACGTAGTCGCGGCGCGCCTCGCC CTTGAGCGTGGAATGAAGCACG Illi GCCCAAGGCGG Illi CGTGCAAAATTCCAAGGTAGGA GACCAGGTTGCAGAGCTCCACGTTGGAGATCTTGCAGGCCTGGCGTACGTAGCCCTGTCGAAA GGTGTAGTGCAATGTTTCCTCTAGCTTGCGCTGCATCTCCGGGTCAGCAAAGAACCGCTGCAT GCACTCAAGCTCCACGGTAACGAGCACTGCGGCCATCATTAGTTTGCGTCGCTCCTCCAAGTC GGCAGGCTCGCGCGTTTGAAGCCAGCGCGCTAGCTGCTCGTCGCCAACTGCGGGTAGGCCCT CCTCTGTTTGTTCTTGCAAATTTGCATCCCTCTCCAGGGGCTGCGCACGGCGCACGATCAGCT CACTCATGACTGTGCTCATGACCTTGGGGGGTAGGTTAAGTGCCGGGTAGGCAAAGTGGGTGA CCTCGATGCTGCG Illi AGTACGGCTAGGCGCGCGTTGTCACCCTCGAGTTCCACCAACACTC CAGAGTGACTTTCA Illi (JGC I G I I I I CCTGTTGCAGAGCGTTTGCCGCGCGCTTCTCGTCGCG TCCAAGACCCTCAAAGATTTTTGGCACTTCGTTGAGCGAGGCGATATCAGGTATGACAGCGCC CTGCCGCAAGGCCAGCTGCTTGTCCGCTCGGCTGCGGTTGGCACGGCAGGATAGGGGTATCT TGCAG Illi GGAAAAAGATGTGATAGGTGGCAAGCACCTCTGGCACGGCAAATACGGGGTAGA AGTTGAGGCGCGGGTTGGGCTCGCATGTGCCG Illi CTTGGCGTTTGGGGGGTACGCGCGGT GAGAATAGGTGGCGTTCGTAGGCAAGGCTGACATCCGCTATGGCGAGGGGCACATCGCTGCG CTCTTGCAACGCGTCGCAGATAATGGCGCACTGGCGCTGCAGATGCTTCAACAGCACGTCGTC TCCCACATCTAGGTAGTCGCCATGCCTTTCGTCCCCCCGCCCGACTTGTTCCTCGTTTGCCTCT GCGTTGTCCTGGTCTTGCTTTTTATCCTCTGTTGGTACTGAGCGGTCCTCGTCGTCTTCGCTTA CAAAACCTGGGTCCTGCTCGATAATCACTTCCTCCTCCTCAAGCGGGGGTGCCTCGACGGGGA AGGTGGTAGGCGCGTTGGCGGCATCGGTGGAGGCGGTGGTGGCGAACTCAGAGGGGGCGGT TAGGCTGTCCTTCTTCTCGACTGACTCCATGATCTTTTTCTGCCTATAGGAGAAGGAAATGGCC AGTCGGGAAGAGGAGCAGCGCGAAACCACCCCCGAGCGCGGACGCGGTGCGGCGCGACGTC CCCCAACCATGGAGGACGTGTCGTCCCCGTCCCCGTCGCCGCCGCCTCCCCGGGCGCCCCC AAAAAAGCGGATGAGGCGGCGTATCGAGTCCGAGGACGAGGAAGACTCATCACAAGACGCGC TGGTGCCGCGCACACCCAGCCCGCGGCCATCGACCTCGGCGGCGGATTTGGCCATTGCGCC CAAGAAGAAAAAGAAGCGCCCTTCTCCCAAGCCCGAGCGCCCGCCATCACCAGAGGTAATCGT GGACAGCGAGGAAGAAAGAGAAGATGTGGCGCTACAAATGGTGGGTTTCAGCAACCCACCGG TGCTAATCAAGCATGGCAAAGGAGGTAAGCGCACAGTGCGGCGGCTGAATGAAGACGACCCA GTGGCGCGTGGTATGCGGACGCAAGAGGAAGAGGAAGAGCCCAGCGAAGCGGAAAGTGAAAT TACGGTGATGAACCCGCTGAGTGTGCCGATCGTGTCTGCGTGGGAGAAGGGCATGGAGGCTG CGCGCGCGCTGATGGACAAGTACCACGTGGATAACGATCTAAAGGCGAACTTCAAACTACTGC CTGACCAAGTGGAAGCTCTGGCGGCCGTATGCAAGACCTGGCTGAACGAGGAGCACCGCGGG TTGCAGCTGACCTTCACCAGCAACAAGACCTTTGTGACGATGATGGGGCGATTCCTGCAGGCG TACCTGCAGTCGTTTGCAGAGGTGACCTACAAGCATCACGAGCCCACGGGCTGCGCGTTGTG GCTGCACCGCTGCGCTGAGATCGAAGGCGAGCTTAAGTGTCTACACGGAAGCATTATGATAAA TAAGGAGCACGTGATTGAAATGGATGTGACGAGCGAAAACGGGCAGCGCGCGCTGAAGGAGC AGTCTAGCAAGGCCAAGATCGTGAAGAACCGGTGGGGCCGAAATGTGGTGCAGATCTCCAACA CCGACGCAAGGTGCTGCGTGCACGACGCGGCCTGTCCGGCCAATCAG Illi CCGGCAAGTCT TGCGGCATGTTCTTCTCTGAAGGCGCAAAGGCTCAGGTGGC Illi AAGCAGAI (JAAGGC I I I IA TGCAGGCGCTGTATCCTAACGCCCAGACCGGGCACGGTCACC Illi GATGCCACTACGGTGCG AGTGCAACTCAAAGCCTGGGCACGCGCCCTTTTTGGGAAGGCAGCTACCAAAGTTGACTCCGT TCGCCCTGAGCAACGCGGAGGACCTGGACGCGGATCTGATCTCCGACAAGAGCGTGCTGGCC AGCGTGCACCACCCGGCGCTGATAGTGTTCCAGTGCTGCAACCCTGTGTATCGCAACTCGCGC GCGCAGGGCGGAGGCCCCAACTGCGACTTCAAGATATCGGCGCCCGACCTGCTAAACGCGTT GGTGATGGTGCGCAGCCTGTGGAGTGAAAACTTCACCGAGCTGCCGCGGATGGTTGTGCCTG AGTTTAAGTGGAGCACTAAACACCAGTATCGCAACGTGTCCCTGCCAGTGGCGCATAGCGATG CGCGGCAGAACCCCTTTGATTTTTAAACGGCGCAGACGGCAAGGGTGGGGGTAAATAATCACC CGAGAGTGTACAAATAAAAGCATTTGCCTTTATTGAAAGTGTCTCTAGTACATTATTTTTACATGT Illi CAAGTGACAAAAAGAAGTGGCGCTCCTAATCTGCGCACTGTGGCTGCGGAAGTAGGGCG AGTGGCGCTCCAGGAAGCTGTAGAGCTGTTCCTGGTTGCGACGCAGGGTGGGCTGTACCTGG GGACTGTTGAGCATGGAGTTGGGTACCCCGGTAATAAGGTTCATGGTGGGGTTGTGATCCATG GGAGTTTGGGGCCAGTTGGCAAAGGCGTGGAGAAACATGCAGCAGAATAGTCCACAGGCGGC CGAGTTGGGCCCCTGTACGCTTTGGGTGGAC Illi CCAGCGTTATACAGCGGTCGGGGGAAGA AGCAATGGCGCTACGGCGCAGGAGTGACTCGTACTCAAACTGGTAAACCTGCTTGAGTCGCTG GTCAGAAAAGCCAAAGGGCTCAAAGAGGTAGCATGTTTTTGAGTGCGGGTTCCAGGCAAAGGC CATCCAGTGTACGCCCCCAGTCTCGGTCCGAGACTCGAACCGGGGGTCCCGCGACTCAACCC TTGGAAAATAACCCTCCGGCTACAGGGAGCGAGCCACTTAATGCTTTCGCTTTCCAGCCTAACC GCTTACGCTGCGCGCGGCCAGTGGCCAAAAAAGCTAGCGCAGCAGCCGCCGCGCCTGGAAG GAAGCCAAAAGGAGCACTCCCCCGTTGTCTGACGTCGCACACCTGGGTTCGACACGCGGGCG GTAACCGCATGGATCACGGCGGACGGCCGGATACGGGGCTCGAACCCCGGTCGTCCGCCAT GATACCCTTGCGAATTTATCCACCAGACCACGGAAGAGTGCCCGCTTACAGGCTCTCC I I I IGC ACGGTAGAGCGTCAACGATTGCGCGCGCCTGACCGGCCAGAGCGTCCCGACCATGGAGCACT Illi GCCGCTGCGCAACATCTGGAACCGCGTCCGCGACTTTCCGCGCGCCTCCACCACCGCC GCCGGCATCACCTGGATGTCCAGGTACATCTACGGATATCATCGCCTTATGTTGGAAGATCTCG CCCCCGGAGCCCCGGCCACCCTACGCTGGCCCCTCTACCGCCAGCCGCCGCCGCACTTTTTG GTGGGATACCAGTACCTGGTGCGGACTTGCAACGACTACGTATTTGACTCGAGGGCTTACTCG CGTCTCAGGTACACCGAGCTCTCGCAGCCGGGTCACCAGACCGTTAACTGGTCCGTTATGGCC AACTGCACTTACACCATCAACACGGGCGCATACCACCGCTTTGTGGACATGGATGACTTCCAGT CTACCCTCACGCAGGTGCAGCAGGCCATATTAGCCGAGCGCGTTGTCGCCGACCTAGCCCTG CTTCAGCCGATGAGGGGCTTCGGGGTCACACGCATGGGAGGAAGAGGGCGCCACCTACGGC CAAACTCCGCCGCCGCCGCAGCGATAGATGCAAGAGATGCAGGACAAGAGGAAGGAGAAGAA GAAGTGCCGGTAGAAAGGCTCATGCAAGACTACTACAAAGACCTGCGCCGATGTCAAAACGAA GCCTGGGGCATGGCCGACCGCCTGCGCATTCAGCAGGCCGGACCCAAGGACATGGTGCTTCT G 2 pAAV2_9 GTCGACGGTATCGGGGGAGCTCGCAGGGTCTCCA Illi GAAGCGGGAGGTTTGAACGCGCAG CCGCCATGCCGGGG I I I IACGAGATTGTGATTAAGGTCCCCAGCGACCTTGACGAGCATCTGC CCGGCATTTCTGACAGCTTTGTGAACTGGGTGGCCGAGAAGGAATGGGAGTTGCCGCCAGATT CTGACATGGATCTGAATCTGATTGAGCAGGCACCCCTGACCGTGGCCGAGAAGCTGCAGCGC GACTTTCTGACGGAATGGCGCCGTGTGAGTAAGGCCCCGGAGGCTC Illi CTTTGTGCAATTT GAGAAGGGAGAGAGCTACTTCCACATGCACGTGCTCGTGGAAACCACCGGGGTGAAATCCAT GG I I I I GGGACGTTTCCTGAGTCAGATTCGCGAAAAACTGATTCAGAGAATTTACCGCGGGATC GAGCCGACTTTGCCAAACTGGTTCGCGGTCACAAAGACCAGAAATGGCGCCGGAGGCGGGAA CAAGGTGGTGGATGAGTGCTACATCCCCAATTACTTGCTCCCCAAAACCCAGCCTGAGCTCCA GTGGGCGTGGACTAATATGGAACAGTATTTAAGCGCCTGTTTGAATCTCACGGAGCGTAAACG GTTGGTGGCGCAGCATCTGACGCACGTGTCGCAGACGCAGGAGCAGAACAAAGAGAATCAGA ATCCCAATTCTGATGCGCCGGTGATCAGATCAAAAACTTCAGCCAGGTACATGGAGCTGGTCG GGTGGCTCGTGGACAAGGGGATTACCTCGGAGAAGCAGTGGATCCAGGAGGACCAGGCCTCA TACATCTCCTTCAATGCGGCCTCCAACTCGCGGTCCCAAATCAAGGCTGCCTTGGACAATGCG GGAAAGATTATGAGCCTGACTAAAACCGCCCCCGACTACCTGGTGGGCCAGCAGCCCGTGGA GGACATTTCCAGCAATCGGATTTATAAAA Illi GGAACTAAACGGGTACGATCCCCAATATGCG GCTTCCGTCTTTCTGGGATGGGCCACGAAAAAGTTCGGCAAGAGGAACACCATCTGGCTGTTT GGGCCTGCAACTACCGGGAAGACCAACATCGCGGAGGCCATAGCCCACACTGTGCCCTTCTA CGGGTGCGTAAACTGGACCAATGAGAACTTTCCCTTCAACGACTGTGTCGACAAGATGGTGAT CTGGTGGGAGGAGGGGAAGATGACCGCCAAGGTCGTGGAGTCGGCCAAAGCCATTCTCGGAG GAAGCAAGGTGCGCGTGGACCAGAAATGCAAGTCCTCGGCCCAGATAGACCCGACTCCCGTG ATCGTCACCTCCAACACCAACATGTGCGCCGTGATTGACGGGAACTCAACGACCTTCGAACAC CAGCAGCCGTTGCAAGACCGGATGTTCAAATTTGAACTCACCCGCCGTCTGGATCATGACTTTG GGAAGGTCACCAAGCAGGAAGTCAAAGACTTTTTCCGGTGGGCAAAGGATCACGTGGTTGAGG TGGAGCATGAATTCTACGTCAAAAAGGGTGGAGCCAAGAAAAGACCCGCCCCCAGTGACGCAG ATATAAGTGAGCCCAAACGGGTGCGCGAGTCAGTTGCGCAGCCATCGACGTCAGACGCGGAA GCTTCGATCAACTACGCGGACAGGTACCAAAACAAATGTTCTCGTCACGTGGGCATGAATCTGA TGCTGTTTCCCTGCAGACAATGCGAGAGACTGAATCAGAATTCAAATATCTGCTTCACTCACGG TGTCAAAGACTGTTTAGAGTGCTTTCCCGTGTCAGAATCTCAACCCGTTTCTGTCGTCAAAAAG GCGTATCAGAAACTGTGCTACATTCATCACATCATGGGAAAGGTGCCAGACGCTTGCACTGCTT GCGACCTGGTCAATGTGGACTTGGATGACTGTGTTTCTGAACAATAAATGACTTAAACCAGGTA TGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTTAGTGAAGGAATTCGCGAGT GGTGGGCTTTGAAACCTGGAGCCCCTCAACCCAAGGCAAATCAACAACATCAAGACAACGCTC GAGGTCTTGTGCTTCCGGGTTACAAATACCTTGGACCCGGCAACGGACTCGACAAGGGGGAG CCGGTCAACGCAGCAGACGCGGCGGCCCTCGAGCACGACAAGGCCTACGACCAGCAGCTCAA GGCCGGAGACAACCCGTACCTCAAGTACAACCACGCCGACGCCGAGTTCCAGGAGCGGCTCA AAGAAGATACGTC Illi GGGGGCAACCTCGGGCGAGCAGTCTTCCAGGCCAAAAAGAGGCTTC TTGAACCTCTTGGTCTGGTTGAGGAAGCGGCTAAGACGGCTCCTGGAAAGAAGAGGCCTGTAG AGCAGTCTCCTCAGGAACCGGACTCCTCCGCGGGTATTGGCAAATCGGGTGCACAGCCCGCT AAAAAGAGACTCAATTTCGGTCAGACTGGCGACACAGAGTCAGTCCCAGACCCTCAACCAATC GGAGAACCTCCCGCAGCCCCCTCAGGTGTGGGATCTCTTACAATGGCTTCAGGTGGTGGCGC ACCAGTGGCAGACAATAACGAAGGTGCCGATGGAGTGGGTAGTTCCTCGGGAAATTGGCATTG CGATTCCCAATGGCTGGGGGACAGAGTCATCACCACCAGCACCCGAACCTGGGCCCTGCCCA CCTACAACAATCACCTCTACAAGCAAATCTCCAACAGCACATCTGGAGGATCTTCAAATGACAA CGCCTACTTCGGCTACAGCACCCCCTGGGGGTA Illi GACTTCAACAGATTCCACTGCCACTTC TCACCACGTGACTGGCAGCGACTCATCAACAACAACTGGGGATTCCGGCCTAAGCGACTCAAC TTCAAGCTCTTCAACATTCAGGTCAAAGAGGTTACGGACAACAATGGAGTCAAGACCATCGCCA ATAACCTTACCAGCACGGTCCAGGTCTTCACGGACTCAGACTATCAGCTCCCGTACGTGCTCG GGTCGGCTCACGAGGGCTGCCTCCCGCCGTTCCCAGCGGACG Illi CATGATTCCTCAGTACG GGTATCTGACGCTTAATGATGGAAGCCAGGCCGTGGGTCGTTCGTCC Illi ACTGCCTGGAAT ATTTCCCGTCGCAAATGCTAAGAACGGGTAACAACTTCCAGTTCAGCTACGAGTTTGAGAACGT ACCTTTCCATAGCAGCTACGCTCACAGCCAAAGCCTGGACCGACTAATGAATCCACTCATCGAC CAATACTTGTACTATCTCTCAAAGACTATTAACGGTTCTGGACAGAATCAACAAACGCTAAAATT CAGTGTGGCCGGACCCAGCAACATGGCTGTCCAGGGAAGAAACTACATACCTGGACCCAGCTA CCGACAACAACGTGTCTCAACCACTGTGACTCAAAACAACAACAGCGAATTTGCTTGGCCTGGA GCTTCTTCTTGGGCTCTCAATGGACGTAATAGCTTGATGAATCCTGGACCTGCTATGGCCAGCC ACAAAGAAGGAGAGGACCGTTTCTTTCCTTTGTCTGGATCTTTAATTTTTGGCAAACAAGGAACT GGAAGAGACAACGTGGATGCGGACAAAGTCATGATAACCAACGAAGAAGAAATTAAAACTACTA ACCCGGTAGCAACGGAGTCCTATGGACAAGTGGCCACAAACCACCAGAGTGCCCAAGCACAG GCGCAGACCGGCTGGGTTCAAAACCAAGGAATACTTCCGGGTATGGTTTGGCAGGACAGAGAT GTGTACCTGCAAGGACCCATTTGGGCCAAAATTCCTCACACGGACGGCAACTTTCACCCTTCTC CGCTGATGGGAGGGTTTGGAATGAAGCACCCGCCTCCTCAGATCCTCATCAAAAACACACCTG TACCTGCGGATCCTCCAACGGCCTTCAACAAGGACAAGCTGAACTCTTTCATCACCCAGTATTC TACTGGCCAAGTCAGCGTGGAGATCGAGTGGGAGCTGCAGAAGGAAAACAGCAAGCGCTGGA ACCCGGAGATCCAGTACACTTCCAACTATTACAAGTCTAATAATGTTGAATTTGCTGTTAATACT GAAGGTGTATATAGTGAACCCCGCCCCATTGGCACCAGATACCTGACTCGTAATCTGTAATTGC TTGTTAATCAATAAACCGTTTAATTCGTTTCAGTTGAACTTTGGTCTCTGCGAAGGGCGAATTCG TTTAAACCTGCAGGACTAGAGGTCCTGTATTAGAGGTCACGTGAGTG Illi GCGACA Illi GCG ACACCATGTGGTCACGCTGGGTATTTAAGCCCGAGTGAGCACGCAGGGTCTCCA Illi GAAGG GGGAGGTTTGAACGCGCAGCCGCCAAGCCGAATTCTGCAGATATCCATCACACTGGCGGCCG CTCGACTAGAGCGGCCGCCACCGCGGTGGAGCTCCAGC Illi GTTCCCTTTAGTGAGGGTTAA TTGCGCGCTTGGCGTAATCATGGTCATAGCTGTTTCCTGTGTGAAATTGTTATCCGCTCACAATT CCACACAACATACGAGCCGGAAGCATAAAGTGTAAAGCCTGGGGTGCCTAATGAGTGAGCTAA CTCACATTAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTG CATTAATGAATCGGCCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCTCTTCCGCTTCC TCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAA GGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGG CCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCC CCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATA AAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCT TACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTG TAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGT TCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGA CTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTG CTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTG CGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAAC CACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCT CAAGAAGATCCTTTGATC Illi CTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAG GGAI I I I GG I GA I GAGA I IA I GAAAAAGGA I G I I (JAGG I AGA I GG I I I IAAATTAAAAATGAAGTT TTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAATGCTTAATCAGTGAG GCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAGTTGCCTGACTCCCCGTCGTGTAGA TAACTACGATACGGGAGGGCTTACCATCTGGCCCCAGTGCTGCAATGATACCGCGAGACCCAC GCTCACCGGCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGT GGTCCTGCAACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTAAGTA GTTCGCCAGTTAATAGTTTGCGCAACGTTGTTGCCATTGCTACAGGCATCGTGGTGTCACGCTC GTCGTTTGGTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCC ATGTTGTGCAAAAAAGCGGTTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCG CAGTGTTATCACTCATGGTTATGGCAGCACTGCATAATTCTCTTACTGTCATGCCATCCGTAAGA TGC Illi CTGTGACTGGTGAGTACTCAACCAAGTCATTCTGAGAATAGTGTATGCGGCGACCGA GTTGCTCTTGCCCGGCGTCAATACGGGATAATACCGCGCCACATAGCAGAACTTTAAAAGTGCT CATCATTGGAAAACGTTCTTCGGGGCGAAAACTCTCAAGGATCTTACCGCTGTTGAGATCCAGT TCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCATC Illi ACTTTCACCAGCGTTTCTGG GTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATAAGGGCGACACGGAAATGTTG AATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTATTGTCTCATGAGCGG ATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTTCCGCGCACATTTCCCCGAAAAG TGCCACCTAAATTGTAAGCGTTAATA HUGH AAAAI I GGGG I I AAA I I I I I GTTAAATCAGCTC ATTTTTTAACCAATAGGCCGAAATCGGCAAAATCCCTTATAAATCAAAAGAATAGACCGAGATAG GGTTGAGTGTTGTTCCAGTTTGGAACAAGAGTCCACTATTAAAGAACGTGGACTCCAACGTCAA AGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTACGTGAACCATCACCCTAATCAAGTTT TTTGGGGTCGAGGTGCCGTAAAGCACTAAATCGGAACCCTAAAGGGAGCCCCCGATTTAGAGC TTGACGGGGAAAGCCGGCGAACGTGGCGAGAAAGGAAGGGAAGAAAGCGAAAGGAGCGGGC GCTAGGGCGCTGGCAAGTGTAGCGGTCACGCTGCGCGTAACCACCACACCCGCCGCGCTTAA TGCGCCGCTACAGGGCGCGTCCCATTCGCCATTCAGGCTGCGCAACTGTTGGGAAGGGCGAT CGGTGCGGGCCTCTTCGCTATTACGCCAGCTGGCGAAAGGGGGATGTGCTGCAAGGCGATTA AGTTGGGTAACGCCAGGG Illi CCCAGTCACGACGTTGTAAAACGACGGCCAGTGAGCGCGC GTAATACGACTCACTATAGGGCGAATTGGGTACCGGGCCCCCCCTCGATCGAG 3 pENN.AAV.cTnT.Pl.S un1-dom-neg CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTG GTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAG GGGTTCCTTGTAGTTAATGATTAACCCGCCATGCTACTTATCTACCAGGGTAATGGGGATCCTC TAGAACTATAGCTAGAATTCGCCCTTACGGGCCCCCCCTCGAGGTCGGGATAAAAGCAGTCTG GGCTTTCACATGACAGCATCTGGGGCTGCGGCAGAGGGTCGGGTCCGAAGCGCTGCCTTATC AGCGCCCCAGCCCTGGGAGGTGACAGCTGGCTGGCTTGTGTCAGCCCCTCGGGCACTCACGT ATCTCCGTCCGACGGGTTTAAAATAGCAAAACTCTGAGGCCACACAATAGCTTGGGCTTATATG GGCTCCTGTGGGGGAAGGGGGAGCACGGAGGGGGCCGGGGCCGCTGCTGCCAAAATAGCAG CTCACAAGTGTTGCATTCCTCTCTGGGCGCCGGGCACATTCCTGCTGGCTCTGCCCGCCCCGG GGTGGGCGCCGGGGGGACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTTCCCAGACAGCCGC CGGCACCCACCGCTCCGTGGGACGATCCCCGAAGCTCTAGAGCTTTATTGCGGTAGTTTATCA CAGTTAAATTGCTAACGCAGTCAGTGCTTCTGACACAACAGTCTCGAACTTAAGCTGCAGAAGT TGGTCGTGAGGCACTGGGCAGGTAAGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAG AAACTGGGCTTGTCGAGACAGAGAAGACTCTTGCGTTTCTGATAGGCACCTATTGGTCTTACTG ACATCCACTTTGCCTTTCTCTCCACAGGTGTCCACTCCCAGTTCAATTACAGCTCTTAAGGCTAG AGTACTTAATACGACTCACTATAGGCTAGCCTCGAGAATTCACGCGGGCCGCCATGAAGTGGG TAACCTTTATTTCCCTTCTTTTTCTCTTTAGCTCGGCCTATTCCAGGGGTGTGTTTCGTCGAGAT GGGCCCGCTTACCCTTACGATGTACCGGATTACGCACTCGACGATTCCAAGGGCATGCATAGA CCTGGCCCTCTTCCCCCGAGCCCACCTCCAAAGGTTGATCACAAGGCTTCCCAGTGGCCTCAG GAGAGTGACATGGGGCAGAAGGTAGCTTCTTTGAGTGCGCAGTGCCACAACCATGATGAGAGA CTTGCAGAGCTGACAGTCCTGCTTCAGAAACTACAGATACGGGTAGACCAAGTGGATGACGGC AGGGAAGGGCTGTCACTGTGGGTCAAGAATGTGGTTGGACAGCACCTGCAGGAGATGGGCAC CATAGAACCACCTGATGCTAAGACTGACTTCATGACTTTCCACCATGACCATGAAGTGCGTCTC TCCAACTTGGAAGATGTTCTTAGAAAACTGACAGAAAAATCTGAGGCTATCCAGAAGGAGCTGG AAGAAACCAAGCTGAAAGCAGGCAGCAGGGATGAAGAGCAGCCCCTCCTTGACCGTGTGCAG CACCTAGAACTGGAACTGAACCTGTTGAAGTCACAGCTGTCAGACTGGCAGCATCTGAAGACC AGCTGTGAGCAGGCTGGGGCCCGCATCCAGGAGACTGTGCAGCTCATGTTCTCTGAGGATCA GCAGGGCGGTTCCCTCGAGTGGCTATTAGAGAAGCTTTCTTCTCGGTTCGTGAGCAAGGATGA GCTGCAGGTGCTCTTACATGACCTTGAGCTGAAACTGCTGCAGAATATCACACACCACATCACC GTGACAGGACAGGCCCCGACATCCGAGGCTATTGTGTCTGCCGTGAATCAGGCAGGGATTTCA GGAATCACAGAAGCGCAAGCACATATCATTGTGAACAATGCTCTGAAGCTGTACTCCCAAGACA AGACGGGGATGGTGGACTTTGCTCTGGAGTCTGGAGGTGGCAGCATCCTAAGCACTCGGTGC TCTGAGACCTATGAGACCAAGACGGCACTGCTGAGCCTGTTTGGGGTCCCACTGTGGTACTTC TCACAGTCACCTCGAGTGGTGATCCAGCCCGACATCTACCCAGGGAATTGCTGGGCGTTCAAA GGTTCCCAGGGGTACCTGGTGGTGCGGTTGTCCATGAAGATCTACCCAACCACATTCACCATG GAACACATTCCAAAGACACTATCACCCACTGGTAACATCTCCAGTGCCCCCAAAGACTTTGCAG TCTATGGACTGGAAACGGAGTATCAAGAAGAGGGGCAGCCTCTGGGACGGTTCACCTATGACC AGGAAGGAGACTCACTCCAGATGTTCCACACACTGGAAAGACCTGACCAAGCCTTCCAGATAG TAGAGCTCCGGGTCCTGTCCAACTGGGGCCACCCTGAGTACACTTGCCTCTACCGGTTCCGAG TCCACGGAGAGCCCATCCAGAAAGATGAGTTGTAGTAAGGTACCTCTAGAGTCGACCCGGGCG GCCTCGAGGACGGGGTGAACTACGCCTGAGGATCCGATCTTTTTCCCTCTGCCAAAAATTATG GGGACATCATGAAGCCCCTTGAGCATCTGACTTCTGGCTAATAAAGGAAATTTA Illi CATTGCA ATAGTGTGTTGGAATTTTTTGTGTCTCTCACTCGGAAGCAATTCGTTGATCTGAATTTCGACCAC CCATAATACCCATTACCCTGGTAGATAAGTAGCATGGCGGGTTAATCATTAACTACAAGGAACC CCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGAC CAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAG CCTTAATTAACCTAATTCACTGGCCGTCG Illi ACAACGTCGTGACTGGGAAAACCCTGGCGTT ACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCC CGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACGCGCCCTGTAG CGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCG CCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCG TCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCC AAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCC CTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAAC CCTATCTCGGTCTATTC I I I I GA I I IAIAAGGGA Illi GCCGATTTCGGCCTATTGGTTAAAAAAT GAGCTGATTTAACAAAAATTTAACGCGAA Illi AACAAAATATTAACGCTTACAATTTAGGTGGC AC I I I I CGGGGAAAI G I GCGCGGAACCCC IAIIIGIIIAIIIII CTAAATACATTCAAATATGTAT CCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTAT TCAACATTTCCGTGTCGCCCTTATTCCC I I I I I I GCGGCA Illi GCCI I CCI G I I I I I GCTCACC CAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG AACTGGATCTCAACAGCGGTAAGATCCTTGAGAG Illi CGCCCCGAAGAACG Illi CCAATGAT GAGCAC Illi AAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCA ACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAG CATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACA CTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACA ACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAA ACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTG GCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGC AGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGG TGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGT AGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGAT AGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTG ATTTAAAACTTCAI I I I IAAI I IAAAAGGAI UIAGG I GAAGAI CC I I I I I GATAATCTCATGACCA AAATCCCTTAACGTGAG Illi CGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATC TTCTTGAGATCC I I I I I I I CTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAG CGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAG AGCGCAGATACCAAATACTGTTCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCT GTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGAT AAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGG CTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGAT ACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTAT CCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCT GGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTC GTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCT TTTGCTGGCC Illi GCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATT ACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGT GAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTC ATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTA ATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTT GTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAGA TTTAATTAAGGCCTTAATTAGG 4 Humanized Sun1 DNpositions 1-3 = start codon; positions 4-84 = signal sequence; positions 88 to 1446 = Sun1; positions 14471458 = KDEL; positions 1459-1461 = stop codon ATGAAGTGGGTAACCTTTATTTCCCTTC I I I I I CTCTTTAGCTCGGCCTATTCCAGGGGTGTGTT TCGTCGAGATGGGCCCGCTCTCGATGACCCCCAGGACGTGTTTAAACCCACGACTTCTCGCCT GAAGCAGCCTCTGCAGGGTGACAGTGAGGC Illi CCGTGGCATTGGATGAGTGGCGTGGAGC AGCAGGTGGCCTCTCTGTCTGGACAGTGCCACCACCATGGTGAGAATCTCCGAGAGCTGACCA CTTTGCTACAGAAGCTGCAGGCTCGGGTGGACCAGATGGAAGGCGGCGCTGCCGGGCCGTCA GCTTCGGTCAGAGACGCTGTGGGACAGCCCCCGAGGGAGACTGACTTTATGGCCTTTCACCAA GAACATGAAGTGCGTATGTCACACTTGGAAGATATTCTGGGAAAACTGAGAGAAAAATCTGAGG CCATCCAGAAGGAACTAGAACAGACCAAGCAAAAAACAATCAGTGCGGTTGGTGAGCAGCTCC TGCCCACAGTCGAGCACCTCCAGCTGGAGCTGGATCAGCTAAAGTCAGAGCTGTCCAGCTGG CGACACGTGAAGACCGGCTGTGAGACAGTGGATGCCGTACAAGAAAGAGTGGACGTGCAAGT CAGAGAAATGGTGAAACTCCTG Illi CCGAAGATCAGCAAGGCGGTTCTCTGGAACAGCTGCT GCAGAGGTTCTCATCACAGTTTGTGAGCAAAGGCGACTTGCAGACGATGCTGCGAGACCTGCA GCTGCAGATCCTGCGGAACGTCACCCACCACGTTTCCGTGACCAAGCAGCTCCCAACCTCAGA AGCCGTGGTGTCTGCTGTGAGCGAGGCGGGGGCGTCTGGAATAACAGAGGCGCAAGCACGT GCCATCGTGAACAGCGCCTTGAAGCTGTATTCCCAAGATAAGACCGGGATGGTGGACTTTGCT CTGGAATCTGGTGGTGGCAGCATCTTGAGTACTCGCTGTTCTGAAACTTACGAAACCAAAACGG CGCTGATGAGTCTGTTTGGGATCCCGCTGTGGTACTTCTCGCAGTCCCCGCGCGTGGTCATCC AGCCTGACATTTACCCCGGTAACTGCTGGGCATTTAAAGGCTCCCAGGGGTACCTGGTGGTGA GGCTCTCCATGATGATCCACCCAGCCGCCTTCACTCTGGAGCACATCCCTAAGACGCTGTCGC CAACAGGCAACATCAGCAGCGCCCCCAAGGACTTCGCCGTCTATGGATTAGAAAATGAGTATC AGGAAGAAGGGCAGCTTCTGGGACAGTTCACGTATGATCAGGATGGGGAGTCGCTCCAGATGT TCCAGGCCCTGAAAAGACCCGACGACACAGCTTTCCAAATAGTGGAACTTCGGATTTTTTCTAA CTGGGGCCATCCTGAGTATACCTGTCTGTATCGGTTCAGAGTTCATGGCGAACCTGTCAAGAAA GATGAGTTGTGA 5 SUN2positions 1-3 = start codon; positions 4-84 = signal sequence; positions 88 to 1467 = Sun2; positions 1468-1479 = KDEL; positions 1480-1482 = stop codon ATGAAGTGGGTAACCTTTATTTCCCTTC I I I I I CTCTTTAGCTCGGCCTATTCCAGGGGTGTGTT TCGTCGAGATGGGCCCGCTCTCGATGAGGGCTGGGAAGCCAGAGACTCATCGCCACATTTCC AGGCTGAGCAGCGTGTTATGTCCCGGGTACACTCTCTGGAGCGGCGTCTGGAAGCTCTTGCTG CTGAA Illi CCTCCAACTGGCAGAAGGAGGCCATGCGGCTGGAACGTCTGGAGCTGCGGCAA GGGGCTCCTGGCCAGGGAGGTGGTGGTGGCCTGAGCCACGAGGACACCCTGGCGCTGCTGG AGGGGCTAGTGAGCCGCCGTGAAGCTGCCCTGAAGGAGGATTTCCGCAGGGAAACTGCTGCT CGCATCCAGGAAGAACTGTCTGCCCTGAGAGCAGAGCATCAGCAAGACTCAGAAGACCTCTTC AAGAAGATCGTCCGGGCCTCCCAGGAGTCCGAGGCTCGCATCCAGCAGCTGAAGTCAGAGTG GCAAAGCATGACCCAGGAGTCCTTCCAGGAGAGCTCTGTGAAGGAGCTGAGGCGGCTGGAGG ACCAGCTGGCCGGCCTGCAGCAGGAGCTGGCGGCTCTGGCACTGAAGCAGAGCTCGGTGGC GGAAGAAGTGGGCCTGCTGCCCCAGCAGATCCAGGCCGTGCGGGACGACGTGGAATCTCAGT TCCCGGCCTGGATCAGTCAGTTCCTTGCCCGAGGTGGAGGGGGCCGCGTGGGGCTCCTTCAG AGAGAGGAGATGCAAGCTCAGCTGCGAGAGCTGGAGAGCAAGATCCTCACCCATGTGGCAGA GATGCAGGGCAAGTCGGCCAGGGAAGCCGCGGCCTCCCTGAGCCTGACGCTGCAGAAAGAA GGTGTGATTGGAGTGACAGAGGAGCAGGTGCACCACATCGTGAAGCAGGCCCTGCAGCGCTA CAGTGAGGACCGCATCGGGCTGGCAGACTACGCCCTGGAGTCAGGAGGGGCCAGCGTCATCA GCACCCGATGTTCTGAGACCTACGAGACCAAGACGGCCCTCCTCAGCCTCTTCGGCATCCCCC TGTGGTACCACTCCCAGTCACCCCGAGTCATCCTCCAGCCAGATGTGCACCCAGGCAACTGCT GGGCCTTCCAGGGGCCACAAGGCTTCGCCGTGGTCCGCCTCTCTGCCCGCATCCGCCCCACA GCCGTTACCTTAGAGCATGTGCCCAAGGCCTTGTCACCCAACAGCACTATCTCCAGTGCCCCC AAGGACTTCGCCATCTTTGGGTTTGACGAAGACCTGCAGCAGGAGGGGACACTCCTTGGCAAG TTCACTTACGATCAGGACGGCGAGCCTATTCAGACGTTTCACTTTCAGGCCCCTACGATGGCCA CGTACCAGGTGGTGGAGCTGCGGATCCTGACTAACTGGGGCCACCCCGAGTACACCTGCATC TACCGCTTCAGAGTGCATGGGGAGCCCGCCCACAAAGATGAGTTGTAG 6 KASH1, derived from Nesprin-1 CGCGGCTTCCTGTTCAGAGTCCTCCGAGCAGCTCTTCCCCTTCAGCTTCTCCTGCTCCTCCTCA TCGGGCTTGCCTGCCTTGTACCAATGTCAGAGGAAGACTACAGCTGTGCCCTCTCCAACAACTT TGCCCGGTCATTCCACCCCATGCTCAGATACACGAATGGCCCTCCTCCACTC 7 KASH1 amino acid sequence RGFLFRVLRAALPLQLLLLLLIGLACLVPMSEEDYSCALSNNFARSFHPMLRYTNGPPPL 8 KASH2, derived from Nesprin-2 CGCTCCTTCCTCTCAAGGGTGGTCCGGGCAGCCCTACCCCTGCAGCTGCTCCTCCTGCTGCTG CTGCTCCTGGCCTGCCTGCTGCCCTCCTCCGAAGAAGACTACAGCTGCACTCAGGCCAACAAC TTTGCCCGGTCC Illi ACCCCATGCTGAGGTACACCAATGGGCCACCCCCCACA 9 KASH2 amino acid sequence RSFLSRWRAALPLQLLLLLLLLLACLLPSSEEDYSCTQANNFARSFYPMLRYTNGPPPT 10 KASH3, derived from Nesprin-3 GGCTCCCTCTTCCGGAGGGCGTGCTGTGTGGCGCTCCCACTGCAGCTGCTTCTGCTGCTGTTC CTCCTCCTGCTGTTCCTGCTCCCAATCAGGGAAGAGGACCGCAGCTGCACCCTGGCCAACAAC TTCGCCCGCTCCTTCACGCTCATGCTGCGCTACAATGGCCCACCACCCACC 11 KASH3 amino acid sequence GSLFRRACCVALPLQLLLLLFLLLLFLLPIREEDRSCTLANNFARSFTLMLRYNGPPPT 12 KASH4, derived from Nesprin-4 GATCCTGCATCCAGGCAGCCTCTGACCTTCCTCCTTATCCTCTTCCTCCTCTTCCTCCTCCTGG TGGGTGCCATGTTTCTCCTGCCCGCGTCAGGAGGCCCCTGCTGCTCTCATGCCCGAATACCCA GGACACCCTACCTGGTGCTCAGCTATGTCAATGGTCTTCCCCCAGTC 13 KASH4 amino acid sequence DPASRQPLTFLLILFLLFLLLVGAMFLLPASGGPCCSHARIPRTPYLVLSYVNGLPPV 14 KASH5, derived from CCDC155 / KASH5 CTCAGAGTCACTCGACATCCACTGATCCCAGCTCCTGTCCTGGGCCTGCTGCTGCTGCTGCTG CTCTCTGTCCTGCTGCTTGGCCCGTCCCCACCTCCCACCTGGCCCCACCTCCAGCTCTGCTAC CTCCAGCCCCCTCCAGTG 15 KASH5 amino acid sequence LRVTRHPLIPAPVLGLLLLLLLSVLLLGPSPPPTWPHLQLCYLQPPPV 16 FLX / FLX-F1 primer CCAGCTTACAGAGCACCGAGCT 17 FLX / FLX-F2 primer TCCTTGCAGTCCCTCTTGCATC 18 FLX / FLX-R1 primer AGGCACCATTGTCACAGGGTC 19 Sun1-F primer GGCAAGTGGATCTCTTGTGAATTCTTGAC 20 Sun1-R primer GTAGCACCCACCTTGGTGAGCTGGTAC 21 Sun1-E8 primer AGCCACATAACCACCTGGAG 22 MyHC-tF primer ATGACAGACAGATCCCTCCTATCTCC 23 MyHC-tR primer CTCATCACTCGTTGCATCATCGAC 24 MyHC-F primer CAAATGTTGCTTGTCTGGTG 25 MyHC-R primer GTCAGTCGAGTGCACAGTTT 26 mcm-3798t primer AGGTGGACCTGATCATGGAG 27 mcm-8346t primer ATACCGGAGATCATGCAAGC 28 mcm-7338 primer CTAGGCCACAGAATTGAAAGATCT 29 mcm-7339 primer GTAGGTGGAAATTCTAGCATCATCC 30 aav Sun1 F primer CGAGAATTCACGCGGGCCGCCATGAAGTGGGTAACCTTTATTTC 31 aav Sun1 R primer CGGGTCGACTCTAGAGGTACCTTACTACAACTCATCTTTCTGGATG 32 aav GFP Sun R primer CGGGTCGACTCTAGAGGTACTTACTACAACTCATCTTTGGATCC 33 Sun1 delSUN RNA guide sequence GCACAATAGCCTCGGATGTCG 34 S...

Claims

1. Use of a LINC complex inhibitor in the manufacture of a medicament for treating or preventing a laminopathy;5 wherein the LINC complex inhibitor is an agent that inhibits formation of a LINC complex, disrupts a LINC complex, or inhibits LINC complex function; andwherein the laminopathy is associated with mutation to LMNA and is not Hutchinson-Gilford Progeria Syndrome.10 2. A method of treating or preventing a laminopathy, comprising administering a therapeutically or prophylactically effective amount of a LINC complex inhibitor to a subject;wherein the LINC complex inhibitor is an agent that inhibits formation of a LINC complex, disrupts a LINC complex, or inhibits LINC complex function; andwherein the laminopathy is associated with mutation to LMNA and is not Hutchinson-15 Gilford Progeria Syndrome.

3. The use according to claim 1, or the method according to claim 2, wherein the laminopathy is characterised by one or more of myopathy, cardiomyopathy, dilated cardiomyopathy, muscular dystrophy, cardiac muscular dystrophy, skeletal muscular dystrophy, progeria, neuropathy,20 lipoatrophy, skeletal dysplasia, lipodystrophy, leukodystrophy or dermopathy.

4. The use or the method according to any one of claims 1 to 3, wherein the laminopathy is selected from: Dilated Cardiomyopathy; Muscular Dystrophy, Congenital, Lmna-Related; Emery-Dreifuss Muscular Dystrophy 2, Autosomal Dominant; Muscular Dystrophy; Mandibuloacral25 Dysplasia with Type a Lipodystrophy; Cardiomyopathy, Dilated, 1a; Charcot-Marie-Tooth Disease; Limb-Girdle Muscular Dystrophy; Cardiomyopathy, Dilated, with Hypergonadotropic Hypogonadism; Emery-Dreifuss Muscular Dystrophy 3, Autosomal Recessive; Lipodystrophy, Familial Partial, Type 2; Emery-Dreifuss Muscular Dystrophy; Charcot-Marie-Tooth Disease, Axonal, Type 2b1; Heart-Hand Syndrome, Slovenian Type; Aging; Familial Partial Lipodystrophy;30 Restrictive Dermopathy, Lethal; Arrhythmogenic Right Ventricular Cardiomyopathy; Tooth Disease; Heart Disease; Werner Syndrome; Hypertrophic Cardiomyopathy; Left Ventricular Noncompaction; Atrioventricular Block; Calcinosis; Acroosteolysis; Autosomal Dominant Limb-Girdle Muscular Dystrophy; Diabetes Mellitus, Noninsulin-Dependent; Osteoporosis; Atrial Fibrillation; Atrial Standstill 1; Acanthosis Nigricans; Cardiac Conduction Defect; Catecholaminergic Polymorphic35 Ventricular Tachycardia; Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy Syndrome; Sick Sinus Syndrome; Pelger-Huet Anomaly; Charcot-Marie-Tooth Disease, Axonal, Type 2e; Congenital Generalized Lipodystrophy; Restrictive Cardiomyopathy; Congenital FiberType Disproportion; Lipodystrophy, Congenital Generalized, Type 1; Myofibrillar Myopathy;2020314333   11 Aug 2026Lipodystrophy, Familial Partial, Type 1; Axonal Neuropathy; Atypical Werner Syndrome; Ovarian Cystadenoma; Fanconi Anemia, Complementation Group a; Body Mass Index Quantitative Trait Locus 11; Skin Disease; Rigid Spine Muscular Dystrophy 1; Neuromuscular Disease; Hallermann-Streiff Syndrome; Bethlem Myopathy 1; Acquired Generalized Lipodystrophy; Cardiomyopathy, 5 Dilated, 1e; Lipodystrophy, Congenital Generalized, Type 4; Undifferentiated PleomorphicSarcoma; Lipodystrophy, Familial Partial, Type 3; Muscular Dystrophy, Congenital Merosin-Deficient, 1a; Proximal Spinal Muscular Atrophy; Muscular Dystrophy-Dystroglycanopathy , Type B, 5; Muscular Dystrophy, Congenital, 1b; Reynolds Syndrome; Wiedemann-Rautenstrauch Syndrome; Emery-Dreifuss Muscular Dystrophy 1, X-Linked; Lipodystrophy, Congenital10 Generalized, Type 2; Monogenic Diabetes; Cardiomyopathy, Dilated, 1d; Myopathy, Proximal, and Ophthalmoplegia; Muscle Tissue Disease; Lipodystrophy, Familial Partial, Type 4;Cardiomyopathy, Dilated, 1h; Second-Degree Atrioventricular Block; Median Neuropathy; Intrinsic Cardiomyopathy; Prolapse of Female Genital Organ; Complete Generalized Lipodystrophy; Rigid Spine Muscular Dystrophy; Emerinopathy; Ulnar Nerve Lesion; Limb-Girdle Muscular Dystrophy15 Type 1b; Lmna-Related Dilated Cardiomyopathy; Pelvic Muscle Wasting; Generalized Lipodystrophy-Associated Progeroid Syndrome; Muscular Disease; Cardiomyopathy, Dilated, 1b; Autosomal Genetic Disease; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Right Dominant Form; Familial Isolated Arrhythmogenic Ventricular Dysplasia, Biventricular Form;Familial Isolated Arrhythmogenic Ventricular Dysplasia, Left Dominant Form; Lmna-Related20 Cardiocutaneous Progeria Syndrome; and Autosomal Semi-Dominant Severe Lipodystrophic Laminopathy.

5. The use or the method according to any one of claims 1 to 4, wherein the LINC complex inhibitor is capable of binding to a LINC complex, a LINC complex protein or an interaction partner25 for a LINC complex protein, or wherein the LINC complex inhibitor is capable of reducing expression of a LINC complex protein.

6. The use or the method according to claim 5, wherein the LINC complex inhibitor is capable of inhibiting interaction between a LINC complex protein and an interaction partner for a LINC30 complex protein.

7. The use or the method according claim 5 or claim 6, wherein the LINC complex inhibitor is a peptide / polypeptide, nucleic acid or small molecule.35 8. The use or the method according to claim 5, wherein the LINC complex inhibitor is capable of modifying a gene encoding a LINC complex protein to reduce its expression.2020314333   11 Aug 20269. The use or the method according to claim 8, wherein the LINC complex inhibitor comprises a site-specific nuclease (SSN) targeting a gene encoding a LINC complex protein.

10. The use or the method according to claim 5, wherein the LINC complex inhibitor is an5 inhibitory nucleic acid capable of reducing expression of a LINC complex protein by RNA interference (RNAi).

11. The use or the method according to any one of claims 5 to 10, wherein the treating or preventing comprises administering nucleic acid encoding the LINC complex inhibitor, or nucleic10 acid encoding factors required for production of the LINC complex inhibitor, to the subject.

12. The use or the method according to claim 10, wherein the inhibitory nucleic acid is a small interfering RNA (siRNA), a short hairpin RNA (shRNA), or a micro RNA (miRNA).15 13. The use or the method according to claim 10 or claim 11, wherein the LINC complex inhibitor is capable of reducing expression of a KASH domain-containing protein or a SUN-domain containing protein.

14. The use or the method according to any one of claims 1 to 7, wherein the LINC complex20 inhibitor is (i) a dominant-negative SUN domain-containing protein that inhibits interaction between a SUN domain-containing protein and a KASH domain-containing protein, or (ii) a dominantnegative KASH domain-containing protein that inhibits interaction between a SUN domaincontaining protein and a KASH domain-containing protein.25 15. The use or the method according to claim 14, wherein the nucleic acid is comprised in a vector, optionally wherein the vector is an adeno-associated viral vector, optionally wherein the adeno-associated viral vector selected from one of the following serotypes: AAV9, AAV1, AAV6, AAV8, AAV2i8, AAV9.45, AAV10 and AAVrh.74.30 16. The use or the method according to claim 15, wherein the vector comprises a promoter providing for expression of the nucleic acid in cardiac and / or skeletal muscle cells or tissue, optionally wherein the promoter is:(i) a cardiac or cardiomyocte-specific promoter, optionally wherein the cardiac or cardiomyocte-specific promoter is selected from a cTNT, a-MHC or MLC2v promoter; or35 (ii) a skeletal muscle or striated muscle cell-specific promoter, optionally wherein the skeletal muscle or striated muscle cell-specific promoter is selected from a MCK, MHCK7 or desmin promoter.

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