METHOD FOR CHARACTERIZING A DNA SAMPLE

Description

FIELD OF INVENTION

[0001] The present invention relates to a method of characterising a DNA sample from a tumour, to determine a prognosis for the tumour, determine the suitability of a treatment for the tumour, select a patient with a tumour for a clinical trial of a cancer therapy, classify patients undergoing treatment for cancer or participating in a clinical trial, and classifying patients who have completed a clinical trial or course of treatment. It is particularly, but not exclusively, concerned with a method for characterising the properties of cancer based on a DNA sample from a tumour.BACKGROUND TO THE INVENTION

[0002] The mutational theory of cancer proposes that changes in DNA sequence, termed "driver" mutations, confer proliferative advantage upon a cell, leading to outgrowth of a neoplastic clone [1]. Some driver mutations are inherited in the germline, but most arise in somatic cells during the lifetime of the cancer patient, together with many "passenger" mutations not implicated in cancer development [1]. Multiple mutational processes, including endogenous and exogenous mutagen exposures, aberrant DNA editing, replication errors and defective DNA maintenance, are responsible for generating these mutations [1-3].

[0003] Over the past five decades, several waves of technology have advanced the characterisation of mutations in cancer genomes. Karyotype analysis revealed rearranged chromosomes and copy number alterations. Subsequently, loss of heterozygosity analysis, hybridisation of cancer-derived DNA to microarrays and other approaches provided higher resolution insights into copy number changes [4-8]. Recently, DNA sequencing has enabled systematic characterisation of the full repertoire of mutation types including base substitutions, small insertions / deletions, rearrangements and copy number changes [9-13], yielding substantial insights into the mutated cancer genes and mutational processes operative in human cancer.

[0004] Alexandrov et al. (Cell Reports vol. 3, no. 1, 1 January 2013, pages 246-259) describes a computational framework to characterise mutational signatures from cancer-derived somatic mutational catalogues, by: (1) classifying single base substitutions (SBS) into six subtypes (C:G>A:T, C:G>G:C, C:G>T:A, T:A>A:T, T:A>C:G and T:A>G:C) then further based on the 5' and 3' sequence context of each mutated base; and (2) identifying mutational signatures as operative processes associated with distributions over the categories of SBS such that the mutations in each category in each of a plurality of cancer genomes can be approximately expressed as the sum of the respective category of all operative processes multiplied by their exposure in the respective cancer genome.

[0005] WO 2013 / 096843 A describes methods for assessing samples for the presence of a loss of heterozygosity (LOH) signature and for predicting the status of homology directed repair (HDR) in a cancer cell, by counting the number of LOH regions within "Indicator LOH regions" that are above a predetermined length but shorter than the entire length of the chromosome in which the LOH regions is located.

[0006] As for many cancer classes, most currently available breast cancer sequences target protein-coding exons [8, 11-15]. Consequently, there has been limited consideration of mutations in untranslated, intronic and intergenic regions, leaving central questions pertaining to the molecular pathogenesis of the disease unresolved. First, the role of activating driver rearrangements [16-18] forming chimeric (fusion) genes / proteins or relocating genes adjacent to new regulatory regions as observed in renal

[19] and haemopoietic malignancies. Second, the role of driver substitutions and indels in non-coding regions of the genome [20, 21]. Common inherited variants conferring susceptibility to human disease are generally in non-coding regulatory regions and the possibility that similar mechanisms operate somatically in cancer was highlighted by the discovery of somatic driver substitutions in the TERT gene promoter [22, 23]. Third, which mutational processes generate the somatic mutations found in breast cancer [2, 24]. Addressing this question has been constrained because exome sequences do not inform on genome rearrangements and capture relatively few base substitution mutations, thus limiting statistical power to extract the mutational signatures imprinted on the genome by these processes [24, 25].

[0007] The present inventors have analysed the complete genome sequences of 560 cases in order to address these and other questions and to pave the way to a comprehensive understanding of the origins and consequences of somatic mutations in breast cancer.

[0008] From this analysis, it has been possible to determine certain characteristics of a cancer tumour based on the mutations found in DNA obtained from that tumour.STATEMENTS OF INVENTION

[0009] The present invention provides a computer-implemented method of determining a prognosis of a tumour or determining the suitability of a treatment for a tumour, the method including characterising a DNA sample obtained from said tumour, by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and determining the prognosis or suitability of the treatment from the interpreted profile.

[0010] The present invention also provides a computer-implemented method of selecting a patient for a clinical trial of a cancer therapy, the method including: characterising a DNA sample obtained from a tumour in said patient, by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and determining whether or not the patient is suitable for the clinical trial on the basis of the profile constructed for that patient.

[0011] The invention also provides a method of classifying a plurality of patients undergoing treatment for cancer, or participating in a clinical trial, the method including allocating patients to groups based on a profile constructed from a DNA sample obtained from a tumour in each patient by a method comprising the steps of: characterising a DNA sample obtained from said tumour, by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e).

[0012] The invention also provides a method of classifying patients who have completed a clinical trial or course of treatment, the method including: by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and correlating the interpreted profile obtained for each patient with the clinical outcome of the trial or treatment.

[0013] A further exemplary embodiment of the present invention provides a computer program product containing non-transitory memory storing a computer program which, when run on a computer, performs the steps of any embodiment of any method of the invention.

[0014] A further exemplary aspect of the present invention provides a computer having a processor, wherein the processor is configured to perform the steps of any embodiment of any method of the invention.BRIEF DESCRIPTION OF THE FIGURES

[0015] Figure 1 is a flow diagram showing, in schematic form, a method of characterising a DNA sample according to an embodiment of the present invention; Figure 2 is a flow diagram showing, in schematic form, a method of determining the likelihood of a DNA sample being HR-deficient or not; Figure 3 shows the catalogue of somatic mutations in 560 breast cancers; Figure 3A is a catalogue of base substitutions, insertions / deletions, rearrangements and driver mutations in the 560 breast cancers (sorted by total substitution burden) with the indel axis limited to 5,000(*); Figure 3B is a complete list of curated driver genes sorted by frequency (descending) and showing the fraction of ER positive (left, total 366) and ER negative (right, total 194) samples carrying a mutation in the relevant driver gene presented in grey along with the log10 p-value of enrichment of each driver gene towards the ER positive or ER negative cohort in black; Figure 4 shows non-coding analyses of breast cancer genomes; Figure 4A shows the distributions of substitution (darker dots, top lines) and indel (lighter dots, bottom lines) mutations within the footprint of five regulatory regions identified as being more significantly mutated than expected is provided on the left, along with the proportion of base substitution mutation signatures associated with corresponding samples carrying mutations in each of these non-coding regions on the right; Figure 4B shows the mutability of TGAACA / TGTTCA motifs within inverted repeats of varying flanking palindromic sequence length compared to motifs not within an inverted repeat; Figure 4C shows the variation in mutability between loci of TGAACA / TGTTCA inverted repeats with 9bp palindromes; Figure 5 shows the extraction and contributions of base substitution signatures in 560 breast cancers; Figure 5A shows twelve mutation signatures extracted using Non-Negative Matrix Factorization with each signature ordered by mutation class (C>A / G>T, C>G / G>C, C>T / G>A, T>A / A>T, T>C / A>G, T>G / A>C), taking immediate flanking sequence into account. For each class, mutations are ordered by 5' base (A,C,G,T) first before 3' base (A,C,G,T); Figure 5B shows the spectrum of base substitution signatures within 560 breast cancers, the mutation signatures are ordered according to broad biological groups: Signatures 1 and 5 are correlated with age of diagnosis, Signatures 2 and 13 are putatively APOBEC-related, Signatures 6, 20 and 26 are associated with MMR deficiency, Signatures 3 and 8 are associated with HR deficiency, Signatures 18, 17 and 30 have unknown etiology; Figure 5C shows the distribution of mutation counts for each signature in relevant breast cancer samples with the percentage of samples carrying each signature provided above each signature; Figure 6 shows the distribution of base substitution signatures in 560 breast cancers; Figure 6A shows the contrasting transcriptional strand asymmetry and replication strand asymmetry between twelve base substitution signatures; Figure 6B shows the six rearrangement signatures extracted using Non-Negative Matrix Factorization with the probability of rearrangement element on y-axis and the rearrangement size on x-axis. Figure 7 shows the rearrangement signatures in the 560 breast cancers as a heatmap of rearrangement signatures (RS) following unsupervised hierarchical clustering based on proportions of RS in each cancer; 7 cluster groups (A-G) were noted and relationships with expression (AIMS) subtype, immunohistopathology status (ER, PR, HER2 status - black=positive), abrogation of BRCA1 and BRCA2 (whether germline, somatic or through promoter hypermethylation), presence of 3 or more foci of kataegis (black=positive), HRD index (top 25% or lowest 25% - black=positive), GISTIC cluster group (black=positive) and driver mutations in cancer genes and miRNA cluster groups with the contribution of base substitution signatures in these 7 cluster groups provided in the lowermost panel; Figure 8 shows a landscape of driver mutations; Figure 8A shows the frequency of driver mutations in breast cancer genes; Figure 8B shows driver mutations by mutation type; Figure 8C shows the distribution of rearrangements throughout the genome including background rearrangement density (continuous line) based on rearrangement breakpoints (in intergenic regions only) and frequency of rearrangement within breast cancer genes (spikes); Figure 9 shows recurrent non-coding events in breast cancers; Figure 9A is a Manhattan plot demonstrating sites with most significant p-values as identified by binning analysis with highlighted sites which were also detected by the method seeking recurrence when partitioned by genomic features; Figure 9B shows the locus at chr11:65Mb which was identified by independent analyses as being more mutated than expected by chance and, in the lowermost panel, a rearrangement hotspot analysis identified this region as a tandem duplication hotspot, with nested tandem duplications noted at this site; partitioning the genome into different regulatory elements, an analysis of substitutions and indels identified IncRNAs MALAT1 and NEAT1 (topmost panels) with significant p-values; Figure 10 shows hotspots of tandem duplications; Figure 10A lists hotspots of tandem duplications; Figure 10B shows ETV6 tandem duplication hotspot occurring in 6 different patients; Figure 11 shows the rearrangement cluster groups and associated features, including Figure 11A, overall survival by rearrangement cluster group; Figure 11B, age of diagnosis; Figure 11C, tumour grade; Figure 11D, menopausal status; Figure 11E, ER status; Figure 11F, immune response metagene panel; Figure 11G, lymphocytic infiltration score; Figure 12 shows the rearrangement breakpoint junctions; Figure 12A is the breakpoint features of rearrangements in the 560 breast cancers sorted by rearrangement signature with non-template sequences to the left of the "blunt" marking and microhomology to the right; Figure 12B shows the breakpoint features in BRCA and non-BRCA cancers; and Figure 13 shows signatures of focal hypermutation; Figure 13A shows kataegis and alternative kataegis occurring at the same locus (ERBB2 amplicon in PD13164a) with the copy number (y-axis) depicted as black dots; lines represent rearrangements breakpoints with the topmost panel showing a ~10Mb region including the ERBB2 locus; the second panel from top zooms in 10-fold to a ~1Mb window highlighting co-occurrence of rearrangement breakpoints, with copy number changes and three different kataegis loci; the third panel from top demonstrates kataegis loci in more detail with log10 intermutation distance on y axis and black arrow highlighting kataegis and light grey blue arrows highlighting alternative kataegis; Figure 13B shows sequence context of kataegis and alternative kataegis identified in this dataset.BRIEF DESCRIPTION OF THE TABLES

[0016] Table 1 sets out a quantitative definition of a number of rearrangement signatures; Table 2 is a summary of the somatic mutation catalogue; Table 3 is a summary of the hunt for novel driver mutations using base substitutions only Table 4 is a summary of the hunt for novel driver mutations using insertions / deletions only Table 5 is a summary of the hunt for novel driver mutations using a combination of base substitutions and insertions / deletions Table 6 is a curated cancer gene list for all cancer types Table 7 is a summary of the hunt for driver mutations from amongst rearrangements Table 8 is the list of driver mutations identified in 560 breast cancers Table 9 is a summary of an analysis searching for predicted in-frame gene fusions, recurrent donors and acceptors Table 10 is a summary of the analysis for recurrent non-coding events. Table 11 is a summary of base substitution and rearrangement mutational signatures and kataegis extracted from 560 breast cancer genomes DETAILED DESCRIPTION

[0017] The methods of the invention comprise characterising a DNA sample obtained from a tumour, the method including three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions and tandem duplications, and (iii) by size of the rearrangement; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour.

[0018] For the avoidance of doubt, the method may include any combination of three or more of the steps a) to e), being: steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); steps c), b) and e); steps a), b), c) and d); steps b), c), d) and e); or all of the steps a) to e).

[0019] In certain embodiments the method further includes the steps of: f) identifying putative recurrently mutated non-coding sites, and using the identified putative recurrently mutated non-coding sites in constructing the interpreted profile.

[0020] In certain embodiments the method further includes the steps of: g) obtaining a biologically useful over-arching summary of the sample, and using the obtained summary in constructing the interpreted profile.

[0021] In certain of those embodiments, step g) includes identifying whether the sample has a high or low likelihood of being homologous recombination (HR)-deficient by performing the steps of: determining the presence or absence of a plurality of base substitution signatures, rearrangement signatures and insertion / deletion (indel) signatures in the sample and copy number profiles for the sample; generating, from the presence or absence of said plurality of base substitution signatures, rearrangement signatures and indel signatures in the sample and the copy number profiles for the sample, a probabilistic score; and based on said probabilistic score, identifying whether said sample has a high or low likelihood of being homologous recombination (HR)-deficient.

[0022] Alternatively, step g) may include identifying whether the sample has a high or low likelihood of being homologous recombination (HR)-deficient by performing the steps of: performing two or more of the following steps: a) determining the presence or absence of at least one base substitution signature in the sample b) determining the presence or absence of at least one rearrangement signature in the sample c) determining the presence or absence of at least one indel signature in the sample; and d) determining a copy number profile for the sample; generating, from the above determinations, a probabilistic score; and based on said probabilistic score, identifying whether said sample has a high or low likelihood of being homologous recombination (HR) -deficient.

[0023] Preferably three or more and more preferably all four of the determining steps of this aspect are performed. The probabilistic score and the weighting of the determinations in generating that probabilistic score may vary depending on which determining steps are performed and / or depending on the number of determining steps performed and / or the number of signatures or profiles used in each determining step.

[0024] Where base substitution signatures are considered, preferably the plurality of base substitution signatures include either base substitution signature 3 or base substitution signature 8 or both.

[0025] Where rearrangement signatures are considered, preferably the plurality of rearrangement signatures includes either rearrangement signature 5 or rearrangement signature 3 or both.

[0026] Where indel signatures are considered, preferably the plurality of indel signatures include microhomology-mediated indels.

[0027] Preferably the copy number profiles, if considered, include the HRD copy number-based index.

[0028] In particular embodiments of the present invention, the plurality of base substitution signatures, the plurality of rearrangement signatures and the plurality of indel signatures consist of base substitution signature 3, base substitution signature 8, rearrangement signature 5 and rearrangement signature 3 and microhomology-mediated indels. Following an extensive study of WGS from breast cancers, these five factors, together with the copy number profile, have been found to have the greatest influence on whether a tumour is HR-deficient or not.

[0029] Preferably in such embodiments, the probabilistic score is a weighted score which gives weight to the factors in the following precedence (greatest first): microhomology-mediated indels, base substitution signature 3, rearrangement signature 5, the HRD copy number-based index, rearrangement signature 3 and base substitution signature 8. The study of WGS from breast cancers found that the above order was indicative of the importance of these six factors.

[0030] The method may further include the step of cataloguing the somatic mutations in said sample to produce a mutational catalogue for that sample, wherein the presence or absence of said base substitution signatures, rearrangement signatures and / or indel signatures as required, is derived from said mutational catalogue.

[0031] When such a catalogue has been obtained, the method may further include the step of determining the number of mutations in the mutational catalogue which are attributable to each of the base substitution signatures, rearrangement signatures and / or indel signatures, as required, which are determined to be present.

[0032] Generating the probabilistic score may include the sub steps of: log-transforming the number of mutations attributed to each of the signatures; normalising the log-transformed number of mutations for each signature and the copy number profile; and weighting each of said normalised values by a predetermined weighting factor which represents the likelihood of the signature or profile associated with that value causing the tumour to be HR deficient.

[0033] By log-transforming the number of mutations and normalising all of the features, an accurate balance between the influence of the various factors can be obtained.

[0034] In one particular embodiment, the probabilistic score is generated as P C i = BRCA = 1 1 + e − β 0 + x i T β where C i is the variable encoding the status of i th< sample β 0 is the intercept weight x i T is the vector encoding features of i th< sample; and β is the vector of weights.

[0035] For embodiments wherein the features consist of the six features set out above, the vector of weights β may be as set out in the table below, or within a variation of ±10%, preferably ±5% of these weights: Featureweight βProportion of indels with micro-homology2.129Number of base substitutions of signature 31.239Number of rearrangement signature 5 rearrangements0.978HRD index0.613Number of rearrangement signature 3 rearrangements0.588Number of base substitutions of signature 80.444

[0036] For other embodiments wherein the features consist of the six features set out above, the vector of weights β may be as set out below in the table below, or within a variation of ±10%, preferably ±5% of these weights: Featureweight βProportion of indels with micro-homology2.398Number of base substitutions of signature 31.611Number of rearrangement signature 5 rearrangements0.847HRD index0.667Number of rearrangement signature 3 rearrangements1.153Number of base substitutions of signature 80.091

[0037] For embodiments wherein the features consist of a subset of the six features set out above, the vector of weights β may be as set out in the table below, or within a variation of ±10%, preferably ±5% of these weights: Feature 1 Weight Feature 2 Weight Number of base substitutions of signature 32.371Number of rearrangement signature 3 rearrangements1.835Number of base substitutions of signature 31.876Number of rearrangement signature 5 rearrangements2.989Number of base substitutions of signature 32.931Proportion of indels with micro-homology3.984Number of base substitutions of signature 32.429HRD index2.051Number of rearrangement signature 3 rearrangements3.559Proportion of indels with micro-homology4.819Number of rearrangement signature 3 rearrangements1.650HRD index1.895Number of rearrangement signature 3 rearrangements2.297Number of base substitutions of signature 80.676Number of rearrangement signature 5 rearrangements3.026Proportion of indels with micro-homology1.933Number of rearrangement signature 5 rearrangements3.715HRD index1.017Proportion of indels with micro-homology2.523HRD index1.894Proportion of indels with micro-homology3.223Number of base substitutions of signature 80.807HRD index2.813Number of base substitutions of signature 80.357

[0038] The step of identifying may include comparing said score to a predetermined threshold and performing said identification based on said comparison. The threshold may be set based on clinical parameters. For example, the weighted score may be compared to a threshold and, from that comparison, a clinical decision as to how to treat a tumour from which the DNA sample was taken can be made.

[0039] The predetermined threshold may be selected in a number of ways. In particular, different thresholds for this determination may be set depending on the context and the desired certainty of the outcome.

[0040] In some embodiments, the threshold will be an absolute number of rearrangements from the rearrangement catalogue of the DNA sample which are determined to be associated with a particular rearrangement signature. If this number is exceeded, then it can be determined that a particular rearrangement signature is present in the DNA sample.

[0041] The rearrangement signatures are generally "additive" with respect to each other (i.e. a tumour may be affected by the underlying mutational processes associated with more than one signature and, if this is the case, a sample from that tumour will generally display a higher overall number of rearrangements (being the sum of the separate rearrangements associated with each of the underlying processes), but with the proportion of rearrangements spread over the signatures which are present). As a result, in determining the presence or absence of a particular signature, attention may focus on the absolute number of rearrangements associated with a particular signature in the sample (which may be calculated by the methods described below in other aspects of the invention). Such thresholds are generally better in situations where multiple signatures are present in a sample.

[0042] In these embodiments, a signature may be determined to be present if at least 5 and preferably at least 10 informative rearrangements are associated with it.

[0043] In other embodiments, the threshold combines the total number of rearrangements detected in the sample (which may be set to ensure that the analysis is representative) along with a proportion of the rearrangements which are associated with a particular signature (again, as determined by the methods described below in other aspects of the invention).

[0044] For example, the requirements for determination that a signature is present may be that there are at least 20, preferably at least 40, more preferably at least 50 informative rearrangements and a signature may be deemed to be present if a proportion of at least 10%, preferably at least 20%, more preferably at least 30% of the rearrangements are associated with it. The higher the number of rearrangements present in a sample, the lower the proportional threshold for detection of a specific signature may be.

[0045] The proportional thresholds may be adjusted depending on the number of other signatures which make up a significant portion of the rearrangements found in the sample (e.g., if 4 signatures are each present with 20-25% of the rearrangements, then it may be determined that all 4 signatures are present, rather than no signatures at all are present), even if the threshold determined under the present embodiments is 30%.

[0046] The above thresholds are based on data obtained from genomes sequenced to 30-40 fold depth. If data is obtained from genomes sequenced at lower coverages, then the number of rearrangements detected overall is likely to be lower, and the thresholds will need to be adjusted accordingly.

[0047] The method may further include the steps of: h) identifying the presence of mis-match repair (MMR) deficiency in the sample by using the presence or absence of base substitution signatures and indel signatures, and using this identification in constructing the interpreted profile.

[0048] The method may further include the steps of: i) identifying mutational characteristics in the sample that are informative of pathophysiological processes that are targetable including signatures relating to the immunological responses or to other DNA damage response processes, and using the identified characteristics in constructing the interpreted profile.

[0049] Preferably the catalogue of base substitution signatures, if obtained, is obtained by: cataloguing the somatic mutations in said sample to produce a mutational catalogue for that sample; determining the contributions of known mutational signatures to said mutational catalogue by determining a scalar factor for each of a plurality of said known mutational signatures which together minimize a function representing the difference between the mutations in said catalogue and the mutations expected from a combination of said plurality of known mutational signatures scaled by said scalar factors; and if the scalar factor corresponding to any one of said mutational signatures exceeds a predetermined threshold, including said mutation signature in the catalogue of base substitution signatures for the sample.

[0050] Preferably the method of this aspect includes the further step of, prior to said step of determining, filtering the mutations in said catalogue to remove either residual germline mutations or known sequencing artefacts or both. Such filtering can be highly advantageous to remove mutations from the catalogue which are known to arise from mechanisms other than somatic mutation, and may therefore cloud or obscure the contributions of the mutational signatures, or lead to false positive results.

[0051] For example, the filtering may use a list of known germline polymorphisms and remove somatic mutations resulting from those polymorphisms from the catalogue prior to determining the contributions of the mutational signatures.

[0052] As a further example, the filtering may use BAM files of unmatched normal human tissue sequenced by the same process as the DNA sample and discard any somatic mutation which is present in at least two well-mapping reads in at least two of said BAM files. This approach can remove artefacts resulting from the sequencing technology used to obtain the sample.

[0053] The method may further include the step of selecting said plurality of known mutational signatures as a subset of all known mutational signatures. By selecting a subset, for example, based on prior knowledge about the sample, the number of possible signatures contributing to the mutational catalogue is reduced, which is likely to increase the accuracy of the determining step.

[0054] For example, the subset of mutational signatures may be selected based on biological knowledge about the DNA sample or the mutational signatures or both. Thus, it may be immediately apparent that a certain DNA sample cannot have resulted from a particular mutational signature as a result of characteristics of the DNA sample and the particular mutational signature. Further possibilities are described in more detail in the embodiments below.

[0055] In particular embodiments, the step of determining may determine the scalars E i which minimize the Frobenius norm: min M → − ∑ i = 1 q S i → × E i 2 F wherein S i and M are equally-sized vectors with nonnegative components being, respectively, a consensus mutational signature and the mutational catalogue and q is the number of signatures in said plurality of known mutational signatures, and wherein E i are further constrained by the requirements that 0 ≤ E i ≤ ∥S i ∥ 1 , i = 1..q, and ∑ i = 1 q E i = S i → 1 .

[0056] Preferably the catalogue of rearrangement signatures, if obtained, is obtained by: cataloguing the somatic mutations in said sample to produce a rearrangement catalogue for that sample which classifies identified rearrangement mutations in the sample into a plurality of categories using said rearrangement classification; determining the contributions of known rearrangement signatures to said rearrangement catalogue by computing the cosine similarity between the rearrangement mutations in said catalogue and the known rearrangement signatures; and if the number or proportion of rearrangements in the rearrangement catalogue which are determined to be associated with one of said rearrangement signatures exceeds a predetermined threshold, including said rearrangement signature in the catalogue of rearrangement signatures for the sample.

[0057] Preferably the method includes the further step of, prior to said step of determining, filtering the mutations in said catalogue to remove either residual germline structural variations or known sequencing artefacts or both. Such filtering can be highly advantageous to remove rearrangements from the catalogue which are known to arise from mechanisms other than somatic mutation, and may therefore cloud or obscure the contributions of the rearrangement signatures, or lead to false positive results.

[0058] For example, the filtering may use a list of known germline rearrangement or copy number polymorphisms and remove somatic mutations resulting from those polymorphisms from the catalogue prior to determining the contributions of the rearrangement signatures.

[0059] As a further example, the filtering may use BAM files of unmatched normal human tissue sequenced by the same process as the DNA sample and discards any somatic mutation which is present in at least two well-mapping reads in at least two of said BAM files. This approach can remove artefacts resulting from the sequencing technology used to obtain the sample.

[0060] The classification of the rearrangement mutations includes identifying mutations as being clustered or non-clustered. This may be determined by a piecewise-constant fitting ("PCF") algorithm which is a method of segmentation of sequential data. In particular embodiments, rearrangements may be identified as being clustered if the average density of rearrangement breakpoints within a segment is a certain factor greater than the whole genome average density of rearrangements for an individual patient's sample. For example the factor may be at least 8 times, preferably at least 9 times and in particular embodiments is 10 times. The inter-rearrangement distance is the distance from a rearrangement breakpoint to the one immediately preceding it in the reference genome. For any given breakpoint, this measurement is already known.

[0061] The classification of the rearrangement mutations includes identifying rearrangements as one of: tandem duplications, deletions, inversions or translocations. Such classifications of rearrangement mutations are already known.

[0062] The classification of the rearrangement mutations further includes grouping mutations identified as tandem duplications, deletions or inversions by size. For example, the mutations may be grouped into a plurality of size groups by the number of bases in the rearrangement. Preferably the size groups are logarithmically based, for example 1-10kb, 10-100kb, 100kb-1Mb, 1Mb-10Mb and greater than 10Mb. Translocations cannot be classified by size.

[0063] In particular embodiments, in each DNA sample the number of rearrangements E i associated with the ith mutational signature S i is determined as proportional to the cosine similarity (C i ) between the catalogue of this sample M and S i : C → i = S → i ⋅ M → S → i M → wherein: E i = C → i ∑ i = 1 q C → i ∑ j = 1 36 M → j wherein S i and M are equally-sized vectors with nonnegative components being, respectively, a known rearrangement signature and the mutational catalogue and q is the number of signatures in said plurality of known rearrangement signatures.

[0064] The method may further include the step of filtering the number of rearrangements determined to be assigned to each signature by reassigning one or more rearrangements from signatures that are less correlated with the catalogue to signatures that are more correlated with the catalogue. Such filtering can serve to reassign rearrangements from a signature which has only a few rearrangements associated with it (and so is probably not present) to a signature which has a greater number of rearrangement associated with it. This can have the effect of reducing "noise" in the assignment process.

[0065] In one embodiment, the step of filtering uses a greedy algorithm to iteratively find an alternative assignment of rearrangements to signatures that improves or does not change the cosine similarity between the catalogue M and the reconstructed catalogue M → ′ = S × E → ij ′ , wherein E → ij ′ is the version of the vector E obtained by moving the mutations from the signature i to signature j, wherein, in each iteration, the effects of all possible movements between signatures are estimated, and the filtering step terminates when all of these possible reassignments have a negative impact on the cosine similarity.

[0066] The subject may be a cancer patient or a suspected cancer patient. For example, the method may be used in the determination or identification of a rearrangement sequence to predict whether the subject has cancer or not or what type of cancer a patient has, or to select the subject for a particular form of treatment.

[0067] The method may further include the step of determining if the number or proportion of rearrangements in the rearrangement catalogue which are determined to be associated with one or more of said rearrangement signatures each or in combination exceeds a predetermined threshold and, if so, determining that said rearrangement signature is present in the sample.

[0068] Preferably the step of identifying driver mutations present in the sample determines whether one or more, preferably at least 50%, preferably 75%, more preferably all of the breast cancer genes from the list of 93 cancer genes in Fig 3C / Table 8 are present or not.

[0069] The DNA samples are preferably obtained from both tumour and normal tissues obtained from the patient, e.g. blood sample from the patient and tumour tissue obtained by a biopsy. Somatic mutations in the tumour sample are detected, standardly, by comparing its genomic sequences with the one of the normal tissue.

[0070] The patient to be treated is preferably a human patient.

[0071] Further aspects of the present invention include computer programs for running on computer systems which carry out the method of the above aspect.

[0072] A further aspect of the present invention provides a computer program product containing non-transitory memory storing a computer program which, when run on a computer, performs three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructs an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and determining the prognosis of the tumour or suitability of a treatment for the tumour from the interpreted profile, or determining whether or not the patient is suitable for a clinical trial of a cancer therapy on the basis of the interpreted profile; or classifying a plurality of patients undergoing treatment for cancer, or participating in a clinical trial, the method including allocating patients to groups based on an interpreted profile constructed from a DNA sample obtained from a tumour in each of said plurality of patients; or classifying patients who have completed a clinical trial or course of treatment, by correlating the interpreted profile obtained for each patient with the clinical outcome of the trial or treatment.

[0073] A further aspect of the present invention provides a computer having a processor, wherein the processor is configured to: perform three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, to construct an interpreted profile of the tumour; , wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and determine the prognosis of the tumour or suitability of a treatment for the tumour from the interpreted profile, or determining whether or not the patient is suitable for a clinical trial of a cancer therapy on the basis of the interpreted profile; or classify a plurality of patients undergoing treatment for cancer, or participating in a clinical trial, the method including allocating patients to groups based on an interpreted profile constructed from a DNA sample obtained from a tumour in each of said plurality of patients; or classify patients who have completed a clinical trial or course of treatment, by correlating the interpreted profile obtained for each patient with the clinical outcome of the trial or treatment.

[0074] The computer program and the processor of the above two aspects may also carry out some or all of the optional or preferred steps described above in relation to the first aspect.

[0075] These and other aspects of the invention are described in further detail below.Uses of Predictor Outcome

[0076] The characterisation (or "genomic profiling") of DNA samples from tumours according to the present disclosure has many uses.

[0077] In particular, it is envisaged that this characterisation will allow for significant advances in the interpretation of clinical outcomes and clinical trials data by allowing the identification of common features amongst those patients who respond to a particular treatment and those who do not. At present little is known about what causes two apparently similar tumours to respond or not to a particular therapy. If the tumours are characterised, either before or after the treatment, differences in the tumours may be identified which allow a profile to be developed of the tumours which respond and which do not.

[0078] Similarly, the characterisation may be used to select or stratify patients for clinical trials by profiling the tumour in advance and conducting the trial only on patients with particular types of tumour, or ensuring that patients with particular types of tumour are considered as a cohort within the trial and their results considered separately from patients with tumours which exhibit different features.

[0079] The characterisation may also be used to guide treatment decisions or in prognosis. In particular, if tumours with particular features or combinations of features are found to respond particularly well or particularly poorly to a certain treatment as a result of studies such as those described in the previous paragraphs, the characterisation may in future be performed in advance of commencing treatment on a patient in order to determine the suitability of that treatment for the patient in question.

[0080] Specifically, aspects of the present invention provide methods of classifying of patients undergoing treatment for cancer, or participating in a clinical trial, based on the profile constructed from a DNA sample obtained from a tumour in the patient by a method according to the above described aspects, including some, all or none of the optional or preferred features of those aspects as described above.

[0081] Further aspects of the present invention provide methods of selecting a patient for a clinical trial of a cancer therapy, the selection being made on the basis of the profile constructed from a DNA sample obtained from a tumour in the patient by a method according to the above described aspects, including some, all or none of the optional or preferred features of those aspects as described above.

[0082] Further aspects of the present invention provide a method of classifying patients who have completed a clinical trial or course of treatment, the method including: characterising a DNA sample obtained from a tumour in each of said patients using a method according to the above described aspects, including some, all or none of the optional or preferred features of those aspects; and correlating the interpreted profile obtained for each patient with the clinical outcome of the trial or treatment as well as a method of determining a prognosis of a tumour, the method including characterising a DNA sample obtained from said tumour using a method according to the above described aspects, including some, all or none of the optional or preferred features of those aspects; and determining the prognosis from the interpreted profile.Genomic profiling to characterise tumour DNA

[0083] The complete genomes of 560 breast cancers and non-neoplastic tissue from different individuals (556 female and four male) were sequenced. 3,479,652 somatic base substitutions, 371,993 small indels and 77,695 rearrangements were detected, with substantial variation in the number of each between individual samples (Figure 3A, Supplementary Table 3). Transcriptome sequence, microRNA expression, array based copy number and DNA methylation data were obtained from subsets of cases.

[0084] To identify new cancer genes, the inventors combined somatic substitutions and indels in protein-coding exons with data from other series [12-15, 26], constituting a total of 1,332 breast cancers, and searched for mutation clustering in each gene beyond that expected by chance. Five cancer genes were found for which evidence was previously absent or equivocal (MED23, FOXP1, MLLT4, XBP1, ZFP36L1), or for which the mutations indicate the gene acts as a recessive cancer gene in breast cancer rather than in a dominant fashion, as previously reported in other cancer types (Supplementary Methods section 7.4 for detailed descriptions). From published reports on all cancer types (http: / / cancer.sanger.ac.uk / census), a list of 727 human cancer genes was compiled (Supplementary Table 12). Based on driver mutations found previously, conservative rules were defined for somatic driver base substitutions and indel mutations in each gene and sought mutations conforming to these rules in the 560 breast cancers. 916 likely driver mutations of these classes were identified (Figure 3B).

[0085] To explore the role of genomic rearrangements as driver mutations [16, 18, 19, 27], the inventors sought predicted in-frame fusion genes that might create activated, dominant cancer genes. 1,278 unique and 39 infrequently recurrent in-frame gene fusions were identified (Supplementary Table 15). Many of the latter, however, were in regions of high rearrangement density, including amplicons

[28] and fragile sites, and their recurrence is likely attributable to chance

[27] . Furthermore, transcriptome sequences from 260 cancers did not show expression of these fusions and generally confirmed the rarity of recurrent in-frame fusion genes. By contrast, recurrent rearrangements interrupting the gene footprints of CDKN2A, RB1, MAP3K1, PTEN, MAP2K4, ARID1B, FBXW7, MLLT4 and TP53 were found beyond the numbers expected from local background rearrangement rates, indicating that they contribute to the driver mutation burden of recessive cancer genes. Several other recurrently rearranged genomic regions were observed, including dominantly-acting cancer genes ETV6 and ESR1 without consistent elevation in expression levels, L1-retrotransposition sites

[29] and fragile sites.

[0086] Incorporation of recurrent copy number changes, including homozygous deletions and amplifications, generated a final tally of 1,628 likely driver mutations in 93 cancer genes (Fig.1C). At least one driver was identifiable in 95% of cancers. The 10 most frequently mutated genes were TP53, PIK3CA, MYC, CCND1, PTEN, ERBB2, chr8:ZNF703 / FGFR1 locus, GATA3, RB1 and MAP3K1 (Figure 3B, Figure 8) and accounted for 62% of drivers.Recurrent somatic mutations in non-coding genomic regions

[0087] To investigate non-coding somatic driver substitutions and indels, the inventors searched for non-coding genomic regions with more mutations than expected by chance (Figure 4A, Supplementary Table 16, Figure 9). The promoter of PLEKHS1 (pleckstrin homology domain containing, family S member 1) exhibited recurrent mutations at two genomic positions

[30] (Fig.2A), the underlined bases in the sequence CAGCAAGC TGAACA GCTTGCTG (as previously reported

[30] ). The two mutated bases are flanked on either side by 9bp of palindromic sequence forming inverted repeats

[31] . Most cancers with these mutations showed many base substitutions of mutational signatures 2 and 13 that have been attributed to activity of APOBEC DNA-editing proteins that target the TCN sequence motif. One of the mutated bases is a cytosine in a TCA sequence context (shown above as the reverse complement, TGA) at which predominantly C>T substitutions were found. The other is a cytosine in ACA context which showed both C>T and C>G mutations.

[0088] The TGAACA core sequence was mutated at the same two positions at multiple locations elsewhere in the genome (Figure 4B) where the TGAACA core was also flanked by palindromes (inverted repeat), albeit of different sequences and lengths (Figure 4B). These mutations were also usually found in cancers with many signature 2 and 13 mutations (Figure 4A). TGAACA core sequences with longer flanking palindromes generally exhibited a higher mutation rate, and TGAACA sequences flanked by 9bp palindromes exhibited a ~265-fold higher mutation rate than sequences without them (Figure 4C). However, additional factors must influence the mutation rate because it varied markedly between TGAACA core sequences with different palindromes of the same length (Figure 4D). Some TGAACA-inverted repeat sites were in regulatory regions but others were intronic or intergenic without functional annotation (examples in Figure 4B) or exonic. The propensity for mutation recurrence at specific positions in a distinctive sequence motif in cancers with numerous mutations of particular signatures renders it plausible that these are hypermutable hotspots [32-34], perhaps through formation of DNA hairpin structures

[35] , which are single stranded at their tips enabling attack by APOBEC enzymes, rather than driver mutations.

[0089] Two recurrently mutated sites were also observed in the promoter of TBC1D12 (TBC1 domain family, member 12) (q-value 4.5e -2< ) (Figure 4A). The mutations were characteristic of signatures 2 and 13 and enriched in cancers with many signature 2 and 13 mutations (Figure 4A). The mutations were within the TBC1D12 Kozak consensus sequence (CCCCAGATG GTGGG)) shifting it away from the consensus

[36] . The association with particular mutational signatures suggests that these may also be in a region of hypermutability rather than drivers.

[0090] The WDR74 (WD repeat domain 74) promoter showed base substitutions and indels (q-value 4.6e -3< ) forming a cluster of overlapping mutations (Figure 4A)

[20] . Coding sequence driver mutations in WDR74 have not been reported. No differences were observed in WDR74 transcript levels between cancers with WDR74 promoter mutations compared to those without. Nevertheless, the pattern of this non-coding mutation cluster, with overlapping and different mutation types, is more compatible with the possibility of the mutations being drivers.

[0091] Two long non-coding RNAs, MALAT1 (q-value 8.7e -11< , as previously reported

[12] ) and NEAT1 (q-value 2.1e -2< ) were enriched with mutations. Transcript levels were not significantly different between mutated and non-mutated samples. Whether these mutations are drivers, or result from local hypermutability, is unclear.Mutational signatures

[0092] Mutational processes generating somatic mutations imprint particular patterns of mutations on cancer genomes, termed signatures [2, 24, 37]. Applying a mathematical approach

[25] to extract mutational signatures previously revealed five base substitution signatures in breast cancer; signatures 1, 2, 3, 8 and 13 [2, 24]. Using this method in the 560 cases revealed 12 signatures, including those previously observed and a further seven, of which five have formerly been detected in other cancer types (signatures 5, 6, 17, 18 and 20) and two are new (signatures 26 and 30) (Figure 5A-B, Figure 6A, Supplementary Table 21A-C, Supplementary Methods 15 for further details). Two indel signatures were also found [2, 24].

[0093] In embodiments of the present invention, detection of the presence of base substitution signatures in a DNA sample obtained from a tumour is carried out using the methods disclosed in

[58] .

[0094] Signatures of rearrangement mutational processes have not previously been formally investigated. To enable this we adopted a rearrangement classification incorporating 32 subclasses. In many cancer genomes, large numbers of rearrangements are regionally clustered, for example in zones of gene amplification. Therefore, the rearrangements were first classified into those inside and outside clusters, further subclassified into deletions, inversions and tandem duplications, and then according to the size of the rearranged segment. The final category in both groups was interchromosomal translocations.

[0095] Application of the mathematical framework used for base substitution signatures [2, 24, 25] extracted six rearrangement signatures (Figure 7A, Supplementary Table 21). Unsupervised hierarchical clustering on the basis of the proportion of rearrangements attributed to each signature in each breast cancer yielded seven major subgroups exhibiting distinct associations with other genomic, histological or gene expression features.

[0096] Rearrangement Signature 1 (9% of all rearrangements) and Rearrangement Signature 3 (18% rearrangements) were characterised predominantly by tandem duplications (Figure 7A). Tandem duplications associated with Rearrangement Signature 1 were mostly >100kb (Figure 7B), and those with Rearrangement Signature 3 <10kb (Figure 7C). More than 95% of Rearrangement Signature 3 tandem duplications were concentrated in 15% of cancers (Cluster D, Figure 7), many with several hundred rearrangements of this type. Almost all cancers (91%) with BRCA1 mutations or promoter hypermethylation were in this group, which was enriched for basal-like, triple negative cancers and copy number classification of a high Homologous Recombination Deficiency (HRD) index [38-40]. Thus, inactivation of BRCA1, but not BRCA2, may be responsible for the Rearrangement Signature 3 small tandem duplication mutator phenotype.

[0097] More than 35% of Rearrangement Signature 1 tandem duplications were found in just 8.5% of the breast cancers and some cases had hundreds of these (Cluster F, Figure 7). The cause of this large tandem duplication mutator phenotype (Figure 7B) is unknown. Cancers exhibiting it are frequently TP53-mutated, relatively late diagnosis, triple-negative breast cancers, showing enrichment for base substitution signature 3 and a high Homologous Recombination Deficiency (HRD) index (Figure 7) but do not have BRCA1 / 2 mutations or BRCA1 promoter hypermethylation.

[0098] Rearrangement Signature 1 (Figure 7B) and 3 (Figure 7C) tandem duplications were generally evenly distributed over the genome. However, there were nine locations at which recurrence of tandem duplications was found across the breast cancers and which often showed multiple, nested tandem duplications in individual cases (Figure 10). These may be mutational hotspots specific for these tandem duplication mutational processes although we cannot exclude the possibility that they represent driver events.

[0099] Rearrangement Signature 5 (accounting for 14% rearrangements) was characterised by deletions <100kb. It was strongly associated with the presence of BRCA1 mutations or promoter hypermethylation (Cluster D, Figure 7, BRCA2 mutations (Cluster G, Figure 7) and with Rearrangement Signature 1 large tandem duplications (Cluster F, Figure 7).

[0100] Rearrangement Signature 2 (accounting for 22% rearrangements) was characterised by non-clustered deletions (>100kb), inversions and interchromosomal translocations, was present in most cancers but was particularly enriched in ER positive cancers with quiet copy number profiles (Cluster E, GISTIC Cluster 3, Figure 8). Rearrangement Signature 4 (accounting for 18% of rearrangements) was characterised by clustered interchromosomal translocations while Rearrangement Signature 6 (19% of rearrangements) by clustered inversions and deletions (Clusters A, B, C, Figure 8).

[0101] Short segments (1-5bp) of overlapping microhomology characteristic of alternative methods of end joining repair were found at most rearrangements [2, 14]. Rearrangement Signatures 2, 4 and 6 were characterised by a peak at 1bp of microhomology while Rearrangement Signatures 1, 3 and 5, associated with homologous recombination DNA repair deficiency, exhibited a peak at 2bp (Figure 12). Thus, different end-joining mechanisms may operate with different rearrangement processes. A proportion of breast cancers showed Rearrangement Signature 5 deletions with longer (>10bp) microhomologies involving sequences from short-interspersed nuclear elements (SINEs), most commonly AluS (63%) and AluY (15%) family repeats (Figure 12). Long segments (more than 10bp) of non-templated sequence were particularly enriched amongst clustered rearrangements.

[0102] As a result of the above, a method for determining the number of rearrangements detected in a DNA sample which are associated with a particular rearrangement signature has also been developed, as set out in more detail in PCT / EP2017 / 060279. In embodiments of the present invention, the detection of rearrangement signatures in a DNA sample from a tumour are carried out according to the methods set out in that application.Microhomology-mediated indels

[0103] The determination of the presence or absence of microhomology-mediated indels (also called "microhomology-mediated deletions" as, of the overall range of insertions and deletions, only deletions are ever classified as microhomology-mediated) can be performed as follows.

[0104] First, indels are identified using cgpPindel, as described in

[59] and

[60] .

[0105] For each insertion / deletion (indel), more than or equal to 25bp of flanking sequence is identified using the Ensembl API.

[0106] Only deletions are taken into consideration for the rest of the analysis. If the first few nucleotides but not all of the nucleotides of the deletion motif matches the first few nucleotides of the immediate 3' flanking sequence, then this is referred to as "microhomology-mediated deletion" or "microhomology-mediated indel".Localised hypermutation: kataegis

[0107] Focal base substitution hypermutation, termed kataegis, is generally characterised by substitutions with characteristic features of signatures 2 and 13 [2, 24]. Kataegis was observed in 49% breast cancers, with 4% exhibiting 10 or more foci (Supplementary Table 21C). Kataegis colocalises with clustered rearrangements characteristic of rearrangement signatures 4 and 6 (Figure 8). Cancers with tandem duplications or deletions of rearrangement signatures 1, 3 and 5 did not usually demonstrate kataegis. However, there must be additional determinants of kataegis since only 2% of rearrangements are associated with it. A rare (14 / 1,557 foci, 0.9%), alternative form of kataegis colocalising with rearrangements but with a base substitution pattern characterised by T>G and T>C mutations predominantly at NTT and NTA sequences was also observed. This pattern of base substitutions most closely matches Signature 9 (http: / / cancer.sanger.ac.uk / cosmic / signatures), previously observed in B lymphocyte neoplasms and attributed to polymerase eta activity

[41] .Mutational signatures associated with BRCA1 and BRCA2 mutations

[0108] Of the 560 breast cancers, 90 had germline (60) or somatic (14) inactivating mutations in BRCA1 (35) or BRCA2 (39) or showed methylation of the BRCA1 promoter (16). Loss of the wild-type chromosome 17 or 13 was observed in 80 / 90 cases. The latter exhibited many base substitution mutations of signature 3, accompanied by deletions of >3bp with microhomology at rearrangement breakpoints, and signature 8 together with CC>AA double nucleotide substitutions. Cases in which the wild type chromosome 17 or 13 was retained did not show these signatures. Thus signature 3 and, to a lesser extent, signature 8 are associated with absence of BRCA1 and BRCA2 functions.

[0109] Cancers with inactivating BRCA1 or BRCA2 mutations usually carry many genomic rearrangements. Cancers with BRCA1, but not BRCA2, mutations exhibit large numbers of Rearrangement Signature 3 small tandem duplications. Cancers with BRCA1 or BRCA2 mutations show substantial numbers of Rearrangement Signature 5 deletions. No other Rearrangement Signatures were associated with BRCA1 or BRCA2 null cases. Some breast cancers without identifiable BRCA1 / 2 mutations or BRCA1 promoter methylation showed these features and segregated with BRCA1 / 2 null cancers in hierarchical clustering analysis (Figure 7). In such cases, the BRCA 1 / 2 mutations may have been missed or other mutated or promoter methylated genes may be exerting similar effects (Please see http: / / cancer.sanger.ac.uk / cosmic / sample / genomes for examples of whole genome profiles of typical BRCA1 null (e.g. PD6413a, PD7215a) and BRCA2 null tumours (e.g. PD4952a, PD4955a)).

[0110] A further subset of cancers (Cluster F, Figure 7) show similarities in mutational pattern to BRCA1 / 2 null cancers, with many Rearrangement Signature 5 deletions and enrichment for base substitution signatures 3 and 8. However, these do not segregate together with BRCA1 / 2 null cases in hierarchical clustering analysis, have Rearrangement Signature 1 large tandem duplications and do not show BRCA1 / 2 mutations. Somatic and germline mutations in genes associated with the DNA double-strand break repair pathway including ATM, ATR, PALB2, RAD51C, RAD50, TP53, CHEK2 and BRIP1, were sought in these cancers. We did not observe any clear-cut relationships between mutations in these genes and these mutational patterns.

[0111] Cancers with BRCA1 / 2 mutations are particularly responsive to cisplatin and PARP inhibitors [43-45]. Combinations of base substitution, indel and rearrangement mutational signatures may be better biomarkers of defective homologous recombination based DNA double strand break repair and responsiveness to these drugs

[46] than BRCA1 / 2 mutations or promoter methylation alone and thus may constitute the basis of future diagnostics.

[0112] As a development of these observations, a method for determining the likelihood of a tumour being HR deficient was developed, as set out in more detail in PCT / EP2017 / 060294. In embodiments of the present invention, the "BRCAness predictor" methods of that application can form an additional part of the characterisation of the tumour.METHODS Sample selection

[0113] DNA was extracted from 560 breast cancers and normal tissue (peripheral blood lymphocytes, adjacent normal breast tissue or skin) from the same individuals. Samples were subjected to pathology review and only samples assessed as being composed of > 70% tumor cells, were accepted for inclusion in the study.Massively-parallel sequencing and alignment

[0114] Short insert 500bp genomic libraries were constructed, flowcells prepared and sequencing clusters generated according to Illumina library protocols

[47] . 108 base / 100 base (genomic), or 75 base (transcriptomic) paired-end sequencing were performed on Illumina GAllx, Hiseq 2000 or Hiseq 2500 genome analyzers in accordance with the Illumina Genome Analyzer operating manual. The average sequence coverage was 40.4 fold for tumour samples and 30.2 fold for normal samples.

[0115] Short insert paired-end reads were aligned to the reference human genome (GRCh37) using Burrows-Wheeler Aligner, BWA (v0.5.9)

[48] .Processing of genomic data

[0116] CaVEMan (Cancer Variants Through Expectation Maximization: http: / / cancerit.github.io / CaVEMan / ) was used for calling somatic substitutions.

[0117] Indels in the tumor and normal genomes were called using a modified Pindel version 2.0. (http: / / cancerit.github.io / cgpPindel / ) on the NCBI37 genome build

[49] .

[0118] Structural variants were discovered using a bespoke algorithm, BRASS (BReakpoint AnalySiS) (https: / / github.com / cancerit / BRASS) through discordantly mapping paired-end reads. Next, discordantly mapping read pairs that were likely to span breakpoints, as well as a selection of nearby properly-paired reads, were grouped for each region of interest. Using the Velvet de novo assembler

[50] , reads were locally assembled within each of these regions to produce a contiguous consensus sequence of each region. Rearrangements, represented by reads from the rearranged derivative as well as the corresponding non-rearranged allele were instantly recognisable from a particular pattern of five vertices in the de Bruijn graph (a mathematical method used in de novo assembly of (short) read sequences) of component of Velvet. Exact coordinates and features of junction sequence (e.g. microhomology or non-templated sequence) were derived from this, following aligning to the reference genome, as though they were split reads.

[0119] Supplementary Table 3 for summary of somatic variants. Annotation was according to ENSEMBL version 58.

[0120] Single nucleotide polymorphism (SNP) array hybridization using the Affymetrix SNP6.0 platform was performed according to Affymetrix protocols. Allele-specific copy number analysis of tumors was performed using ASCAT (v2.1.1), to generate integral allele-specific copy number profiles for the tumor cells

[51] . ASCAT was also applied to NGS data directly with highly comparable results.Identification of novel breast cancer genes

[0121] To identify recurrently mutated driver genes, a dN / dS method that considers the mutation spectrum, the sequence of each gene, the impact of coding substitutions (synonymous, missense, nonsense, splice site) and the variation of the mutation rate across genes [52, 53] was used for substitutions (Supplementary Table 9). Owing to the lack of a neutral reference for the indel rate in coding sequences, a different approach was required (Supplementary Table 10, Supplementary Methods for details). To detect genes under significant selective pressure by either point mutations or indels, for each gene the P-values from the dN / dS analysis of substitutions and from the recurrence analysis of indels were combined using Fisher's method. Multiple testing correction (Benjamini-Hochberg FDR) was performed separately for the 600+ putative driver genes and for all other genes, stratifying the FDR correction to increase sensitivity (as described in Sun et al. 2006

[54] ). To achieve a low false discovery rate a conservative q-value cutoff of <0.01 was used for significance (Supplementary Table 11).

[0122] This analysis was applied to the 560 whole genome sequenced breast cancers as well as a further 772 breast cancers that have been sequenced previously by other institutions.

[0123] Please see Supplementary Methods for detailed explanations of these methods.Recurrence in the non-coding regions Partitioning the genome into functional regulatory elements / gene features

[0124] To identify non-coding regions with significant recurrence, the inventors used a method similar to the one described for searching for novel indel drivers.

[0125] The genome was partitioned according to different sets of regulatory elements / gene features, with a separate analysis performed for each set of elements, including exons (n=20,245 genes), core promoters (n=20,245 genes, where a core promoter is the interval [-250,+250] bp from any transcription start site (TSS) of a coding transcript of the gene, excluding any overlap with coding regions), 5' UTR (n=9,576 genes), 3' UTR (n=19,502 genes), intronic regions flanking exons (n=20,212 genes, represents any intronic sequence within 75bp from an exon, excluding any base overlapping with any of the above elements. This attempts to capture recurrence in essential splice site or proximal splicing-regulatory elements), any other sequence within genes (n=18,591 genes, for every protein-coding gene, this contains any region within the start and end of transcripts not included in any of the above categories), ncRNAs (n=10,684, full length lincRNAs, miRNAs or rRNAs), enhancers (n=194,054)

[55] , ultra-conserved regions (n=187,057, a collection of regions under negative selection based on 1,000 genomes data

[20] .

[0126] Every element set listed above was analysed separately to allow for different mutation rates across element types and to stratify the FDR correction

[54] . Within each set of elements, a negative binomial regression approach was used to learn the underlying variation of the mutation rate across elements. The offset reflects the expected number of mutations in each element assuming uniform mutation rates across them (i.e. E subs,element = Σ j∈{1,2,...,192} (t*r j *S j ), and, E indels,element = µ indel * S indel,element ). As covariate here the local density of mutations in neighbouring non-coding regions was used, corrected for sequence composition and trinucleotide mutation rates, that is, the t parameter of the dN / dS equations. Normalised local rates were pre-calculated for 100kb non-overlapping bins of the genome and used in all analyses. Other covariates (expression, replication time or HiC) were not used here as they were not found to substantially improve the model once the local mutation rate was used as a covariate. A separate regression analysis was performed for substitutions and indels, to account for the different level of uncertainty in the distribution of substitution and indel rates across elements. model subs = glm . nb formula = n subs ∼ offset log E subs + μ local , subs model indels = glm . nb formula = n indels ∼ offset log E indels + μ local , indels

[0127] The observed counts for each element (n subs,element and n indels,element ) are compared to the background distributions using a negative binomial test, with the estimated overdispersion parameters (θ subs and θ indels ) estimated by the negative binomial regression, yielding P-values for substitution and indel recurrence for each element. These P-values were combined using Fisher's method and corrected for multiple testing using FDR (Supplementary Table 16A).Partitioning the genome into discrete bins

[0128] A genome-wide screening of recurrence in 1kb non-overlapping bins was performed. The method described in the earlier section was employed, using as covariate the local mutation rate calculated from 5Mb up and downstream from the bin of interest and excluding any low-coverage region from the estimate (Supplementary Table 16B, Figure 9A for example). Significant hits were subjected to manual curation to remove false positives caused by sequencing or mapping artefacts.Mutational signatures analysis

[0129] Mutational signatures analysis was performed following a three-step process: (i) hierarchical de novo extraction based on somatic substitutions and their immediate sequence context, (ii) updating the set of consensus signatures using the mutational signatures extracted from breast cancer genomes, and (iii) evaluating the contributions of each of the updated consensus signatures in each of the breast cancer samples. These three steps are discussed in more detail in the next sections.Hierarchical de novo extraction of mutational signatures

[0130] The mutational catalogues of the 560 breast cancer whole genomes were analysed for mutational signatures using a hierarchical version of the Wellcome Trust Sanger Institute mutational signatures framework

[25] . Briefly, we converted all mutation data into a matrix, M, that is made up of 96 features comprising mutations counts for each mutation type (C>A, C>G, C>T, T>A, T>C, and T>G; all substitutions are referred to by the pyrimidine of the mutated Watson-Crick base pair) using each possible 5' (C, A, G, and T) and 3' (C, A, G, and T) context for all samples. After conversion, the previously developed algorithm was applied in a hierarchical manner to the matrix M that contains K mutation types and G samples. The algorithm deciphers the minimal set of mutational signatures that optimally explains the proportion of each mutation type and then estimates the contribution of each signature across the samples. More specifically, the algorithm makes use of a well-known blind source separation technique, termed nonnegative matrix factorization (NMF). NMF identifies the matrix of mutational signature, P, and the matrix of the exposures of these signatures, E, by minimizing a Frobenius norm while maintaining non-negativity: min P ∈ M ℝ + K ˙ N E ∈ M ℝ + N G M − P × E F 2

[0131] The method for deciphering mutational signatures, including evaluation with simulated data and list of limitations, can be found in

[25] . The framework was applied in a hierarchical manner to increase its ability to find mutational signatures present in few samples as well as mutational signatures exhibiting a low mutational burden. More specifically, after application to the original matrix Mcontaining 560 samples, we evaluated the accuracy of explaining the mutational patterns of each of the 560 breast cancers with the extracted mutational signatures. All samples that were well explained by the extracted mutational signatures were removed and the framework was applied to the remaining sub-matrix of M. This procedure was repeated until the extraction process did not reveal any new mutational signatures. Overall, the approach extracted 12 unique mutational signatures operative across the 560 breast cancers (Figure 5, Supplementary Table 21).Updating the set of consensus mutational signatures

[0132] The 12 hierarchically extracted breast cancer signatures were compared to the census of consensus mutational signatures

[25] . 11 of the 12 signatures closely resembled previously identified mutational patterns. The patterns of these 11 signatures, weighted by the numbers of mutations contributed by each signature in the breast cancer data, were used to update the set of consensus mutational signatures as previously done in

[25] . 1 of the 12 extracted signatures is novel and at present, unique for breast cancer. This novel signature is consensus signature 30 (http: / / cancer.sanger.ac.uk / cosmic / signatures).Evaluating the contributions of consensus mutational signatures in 560 breast cancers

[0133] The complete compendium of consensus mutational signatures that was found in breast cancer includes: signatures 1, 2, 3, 5, 6, 8, 13, 17, 18, 20, 26, and 30. We evaluated the presence of all these signatures in the 560 breast cancer genomes by re-introducing them into each sample. More specifically, the updated set of consensus mutational signatures was used to minimize the constrained linear function for each sample: min Exposures i ≥ 0 SampleMutations − ∑ i = 1 N Signature i → ∗ Exposure i F 2

[0134] Here, Signature i represents a vector with 96 components (corresponding to a consensus mutational signature with its six somatic substitutions and their immediate sequencing context) and Exposure i is a nonnegative scalar reflecting the number of mutations contributed by this signature. N is equal to 12 and it reflects the number of all possible signatures that can be found in a single breast cancer sample. Mutational signatures that did not contribute large numbers (or proportions) of mutations or that did not significantly improve the correlation between the original mutational pattern of the sample and the one generated by the mutational signatures were excluded from the sample. This procedure reduced over-fitting the data and allowed only the essential mutational signatures to be present in each sample (Supplementary Table 21B).Kataegis

[0135] Kataegis or foci of localized hypermutation has been previously defined

[25] as 6 or more consecutive mutations with an average intermutation distance of less than or equal to 1,000 bp. Kataegis were sought in 560 whole-genome sequenced breast cancers from high-quality base substitution data using the method described previously

[25] . This method likely misses some foci of kataegis sacrificing sensitivity of detection for a higher positive predictive value of kataegic foci (Supplementary Table 21C).Rearrangement signatures Clustered vs non-clustered rearrangements

[0136] Rearrangements that occurred as focal catastrophic events or focal driver amplicons were separated from genome-wide rearrangement mutagenesis using a piecewise constant fitting (PCF) method. For each sample, both breakpoints of each rearrangement were considered individually and all breakpoints were ordered by chromosomal position. The inter-rearrangement distance, defined as the number of base pairs from one rearrangement breakpoint to the one immediately preceding it in the reference genome, was calculated. Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distance that was at least 10 times greater than the whole genome average for the individual sample. PCF parameters used were γ = 25 and kmin = 10. The respective partner breakpoint of all breakpoints involved in a clustered region are likely to have arisen at the same mechanistic instant and so were considered as being involved in the cluster even if located at a distant chromosomal site. Extended Data Table 4A summarises the rearrangements within clusters ("clustered") and not within clusters ("non-clustered").Classification - types and size

[0137] In both classes of rearrangements, clustered and non-clustered, rearrangements were subclassified into deletions, inversions and tandem duplications, and then further subclassified according to size of the rearranged segment (1-10kb, 10kb-100kb, 100kb-1Mb, 1Mb-10Mb, more than 10Mb). The final category in both groups was interchromosomal translocations.Rearrangement signatures by NNMF

[0138] The classification produces a matrix of 32 distinct categories of structural variants across 544 breast cancer genomes. This matrix was decomposed using the previously developed approach for deciphering mutational signatures by searching for the optimal number of mutational signatures that best explains the data without over-fitting the data

[25] (Supplementary Table 21D-E).Consensus clustering of rearrangement signatures

[0139] To identify subgroups of samples sharing similar combinations of six identified rearrangement signatures derived from whole genome sequencing analysis consensus clustering was performed using the ConsensusClusterPlus R package

[56] . Input data for each sample (n=544, a subset of the full sample cohort) was the proportion of rearrangements assigned to each of the six signatures. Thus, each sample has 6 data values, with a total sum of 1. Proportions for each signature were mean-centred across samples prior to clustering. The following settings were used in the consensus clustering: Number of repetitions: 1000 pltem = 0.9 (resampling frequency samples) pFeature = 0.9 (resampling frequency) Pearson distance metric Ward linkage method Individual patient whole genome profiles

[0140] Breast cancer whole genome profiles were adapted from the R Circos package

[57] . Features depicted in circos plots from outermost rings heading inwards: Karyotypic ideogram outermost. Base substitutions next, plotted as rainfall plots (log10 intermutation distance on radial axis, dot colours: blue=C>A, black=C>G, red=C>T, grey=T>A, green=T>C, pink=T>G). Ring with short green lines = insertions, ring with short red lines = deletions. Major copy number allele (green = gain) ring, minor copy number allele ring (pink=loss), Central lines represent rearrangements (green= tandem duplications, pink=deletions, blue=inversions and gray=interchromosomal events. Top right hand panel displays the number of mtations contributing to each mutation signature extracted using NNMF in individual cancers. Middle right hand panel represents indels. Bottom right corner shows histogram of rearrangements present in this cancer. Bottom left corner shows all curated driver mutations, top and middle left panels show clinical and pathology data respectively.

[0141] The systems and methods of the above embodiments may be implemented in a computer system (in particular in computer hardware or in computer software) in addition to the structural components and user interactions described.

[0142] The term "computer system" includes the hardware, software and data storage devices for embodying a system or carrying out a method according to the above described embodiments. For example, a computer system may comprise a central processing unit (CPU), input means, output means and data storage. Preferably the computer system has a monitor to provide a visual output display (for example in the design of the business process). The data storage may comprise RAM, disk drives or other computer readable media. The computer system may include a plurality of computing devices connected by a network and able to communicate with each other over that network.

[0143] The methods of the above embodiments may be provided as computer programs or as computer program products or computer readable media carrying a computer program which is arranged, when run on a computer, to perform the method(s) described above.

[0144] The term "computer readable media" includes, without limitation, any non-transitory medium or media which can be read and accessed directly by a computer or computer system. The media can include, but are not limited to, magnetic storage media such as floppy discs, hard disc storage media and magnetic tape; optical storage media such as optical discs or CD-ROMs; electrical storage media such as memory, including RAM, ROM and flash memory; and hybrids and combinations of the above such as magnetic / optical storage media. TABLE 1Probability Type Class Size Signature 1 Signature 2 Signature 3 Signature 4 Signature 5 Signature 6 clustereddeletion1-10kb0%0%0%1%0%1%clustereddeletion10-100kb0%0%0%1%0%1%clustereddeletion100kb-1Mb0%0%0%2%0%3%clustereddeletion1Mb-10Mb0%0%0%3%0%7%clustereddeletion>10Mb0%0%0%1%0%7%clusteredtandem duplication1-10kb0%0%0%0%0%0%clusteredtandem duplication10-100kb0%0%0%1%0%1%clusteredtandem duplication100kb-1Mb1%0%0%1%0%3%clusteredtandem duplication1Mb-10Mb0%0%0%3%0%7%clusteredtandem duplication>10Mb0%0%0%1%0%7%clusteredinversion1-10kb0%0%0%3%0%2%clusteredinversion10-100kb0%0%0%2%0%2%clusteredinversion100kb-1Mb0%0%0%3%0%5%clusteredinversion1Mb-10Mb0%0%0%6%0%15%clusteredinversion>10Mb0%0%0%2%0%14%clusteredtranslocation0%0%0%56%0%0%non-clustereddeletion1-10kb0%2%2%0%32%3%non-clustereddeletion10-100kb1%1%0%0%22%2%non-clustereddeletion100kb-1Mb4%5%0%0%5%2%non-clustereddeletion1Mb-10Mb1%6%0%1%1%2%non-clustereddeletion>10Mb0%6%1%0%1%2%non-clusteredtandem duplication1-10kb0%0%53%0%1%0%non-clusteredtandem duplication10-100kb16%0%22%0%12%0%non-clusteredtandem duplication100kb-1Mb54%0%1%0%1%0%non-clusteredtandem duplication1Mb-10Mb17%2%0%1%0%1%non-clusteredtandem duplication>10Mb0%5%1%0%1%1%non-clusteredinversion1-10kb1%5%1%1%5%1%non-clusteredinversion10-100kb2%2%0%0%3%1%non-clusteredinversion100kb-1Mb2%4%0%0%0%1%non-clusteredinversion1Mb-10Mb0%10%0%1%0%4%non-clusteredinversion>10Mb1%12%1%0%2%3%non-clusteredtranslocation1%39%16%7%13%1% Table 2 samplesubstitutionsinsertion / deletionsrearrangementsPD10010a2431205108PD10011a8272246144PD10014a12125633221PD11326a9628491360PD11327a12715350274PD11336a558521574PD11337a307321377PD11338a23002212PD11339a252930063PD11340a5064445349PD11341a16528140PD11342a330517317PD11343a2944148122PD11344a11028122165PD11345a10351495451PD11346a2292174471PD11347a2031146146PD11348a5010262130PD11349a7449424451PD11352a25862212PD11355a183819242PD11357a337943518PD11358a43273040PD11359a26662451PD11360a311627487PD11361a17231115PD11364a233921423PD11365a13652308827PD11366a300530632PD11367a8164418104PD11368a6828495333PD11369a6134438308PD11370a12791063PD11372a1379337057PD11374a238315770PD11375a19341467PD11376a315229364PD11379a19382436115PD11380a272031432PD11381a209719129PD11383a25792434PD11384a17251315PD11385a188717276PD11386a338220916PD11388a4989270156PD11389a16772051PD11391a12741052PD11393a4669299157PD11394a220921226PD11395a379236625PD11396a243523446PD11397a4827223100PD11398a234715043PD11399a3496185125PD11402a263623631PD11462a2839392149PD11464a4497144154PD11465a22551762208PD11740a233418415PD11741a197610434PD11742a7005581334PD11743a330919282PD11744a18821391PD11745a3018169154PD11748a11761462401PD11750a10078264217PD11751a166481074513PD11752a7636458246PD11753a685837210PD11755a2776117130PD11756a177111317PD11757a19524094PD11760a409133876PD11761a270716370PD11762a173410516PD11765a200210642PD11766a16959081PD11767a869486PD11769a172219653PD11816a401122257PD11818a1605108301PD11819a16861012PD13162a5404198136PD13163a5353649172PD13164a272221385PD13165a6341371324PD13166a2331274172PD13167a2405158242PD13168a2528116178PD13296a185829701221PD13297a14982947322PD13298a8367536233PD13299a10735497278PD13302a4896425267PD13304a15171790PD13306a202613118PD13307a535321378PD13310a18311911PD13311a451091145PD13312a203427821PD13416a19391820PD13418a680828849PD13419a10927425PD13420a186212516PD13422a180517810PD13424a3954259217PD13425a34502719617PD13426a26992390PD13427a1134902PD13428a342228349PD13602a5914446231PD13603a3064224309PD13604a93102586148PD13605a1238108162PD13606a5893589336PD13607a328826440PD13608a4107186175PD13609a4706143478PD13618a18331070PD13619a21121882PD13620a4598640156PD13622a4355258256PD13623a380019810PD13625a11239714242PD13626a107610138PD13627a8442276184PD13629a20291762PD13630a410721685PD13631a260314619PD13752a280923158PD13753a799512411PD13754a250613720PD13755a19361551PD13756a20832050PD13757a14874824PD13758a229918825PD13760a463418610PD13761a16881651PD13762a16531451PD13763a256319967PD13764a4830166989PD13765a5479386108PD13766a383712167PD13767a263820625PD13768a13521401PD13770a207910634PD13771a13089845280PD14432a187019213PD14433a358223154PD14435a3716273200PD14437a4363258217PD14439a13161545PD14441a466225532PD14442a17461162PD14450a129810245PD14453a9916498318PD14454a2510122129PD14456a197713926PD14457a4567262182PD14458a15131530PD14459a208616431PD14460a452422058PD14461a143613738PD14462a262815229PD14465a309725799PD14467a162411252PD14468a154915215PD14471a3270245115PD14472a22982207PD14473a15439038PD17973a202514114PD17981a696431844PD17991a12221213PD17994a1306627PD18017a210811460PD18020a17772336446PD18022a160274113PD18024a11104340667PD18031a276917393PD18037a5971455197PD18045a19468506570PD18046a290152839PD18047a234424688PD18048a4786316198PD18049a339223150PD18050a3566185299PD18100a1531908PD18101a863679PD18116a15441129PD18149a257029321PD18188a223613952PD18189a427223973PD18247a91361103PD18251a3487175125PD18257a297313051PD18258a11421198PD18259a663941978PD18264a668012240PD18269a1387942PD18728a17691662PD18730a19019420PD18733a301925833PD18734a3828188318PD18748a295815219PD18749a46611502PD18751a190711971PD18754a259317621PD18756a16351012PD18768a25562362PD18769a29827621PD18771a17761208PD18775a13308411PD18776a162911513PD22036a1047340PD22251a150512439PD22355a9761632473PD22357a7719298276PD22358a615812361PD22359a18177633PD22360a8510150154PD22361a5899236129PD22362a194959158PD22363a8905332132PD22364a240215240PD22365a19066049PD22366a9809388260PD23550a2866113271PD23554a6899102131PD23558a10134620148PD23559a538220484PD23560a300611777PD23561a58028253574PD23562a7348448221PD23563a8223317215PD23564a83447667649PD23565a8852252174PD23566a6667289265PD23567a7198381255PD23569a10553321PD23570a224512028PD23574a13094386326PD23577a3970309199PD23578a6840195220PD23579a87311558499PD24182a9537293196PD24186a7488238113PD24189a29590359718PD24190a9808381226PD24191a612065656PD24192a178271017225PD24193a1123742822PD24194a1369522051PD24195a22407714PD24196a262081142PD24197a20215423319PD24199a285464131PD24200a9741947PD24201a204781095389PD24202a7779332292PD24204a27952015PD24205a892878183PD24206a3610164104PD24207a4745201347PD24208a2562413062PD24209a1016920973PD24212a10055807235PD24214a3079212213PD24215a617767863PD24216a933923259PD24217a1530544110PD24218a328835095PD24219a3319169100PD24220a3611273383PD24221a229310312PD24223a342818512PD24224a22129043PD24225a18215131PD24302a1268885PD24303a450069165PD24304a685318591PD24306a333681107PD24307a15948950PD24308a4752290221PD24314a3870182143PD24318a254616294PD24320a15695384061PD24322a486820298PD24325a10387479200PD24326a2362025261PD24327a16185253247PD24329a211115294PD24332a192010479PD24333a2288439649PD24335a3948246434PD24336a333918081PD24337a5707360460PD3851a18198432PD3890a5584170166PD3904a5668649161PD3905a4603124139PD3945a10551500104PD3989a223814914PD4005a6041151184PD4006a9575288351PD4069a20852053PD4072a279311351PD4076a20911232PD4085a270411066PD4086a19516849PD4088a169177171PD4103a5218266613PD4107a9874389291PD4109a10313840181PD4115a9752821129PD4116a8170486256PD4192a429272102PD4194a14283423PD4198a4517185220PD4199a694813385PD4225a195518546PD4248a2196136141PD4252a3773431150PD4255a4554383311PD4261a179613824PD4264a211814870PD4266a23881377PD4267a21191130PD4315a3388195209PD4604a9323354201PD4605a265018798PD4606a11297248PD4607a2595315718PD4613a219510924PD4826a3818260293PD4833a6401626540PD4836a430331780PD4841a7020461607PD4844a128101065216PD4845a5735439155PD4847a110421314252PD4872a481022490PD4874a9709240222PD4875a6805310138PD4876a490832595PD4951a277920033PD4952a120331069333PD4953a6946355143PD4954a5764371127PD4955a6070736102PD4956a11582917236PD4957a327917174PD4958a9338486102PD4959a4611370103PD4962a684314385PD4965a270617633PD4967a32271139PD4968a4780327213PD4969a10326318PD4970a241012631PD4971a2765110383PD4972a1145860PD4975a750623476PD4976a6275471118PD4977a4225850016PD4978a3736155555PD4980a379636487PD4981a16631162PD4982a14741560PD4983a17631280PD4985a20041732PD4986a19764999PD5925a878027692PD5928a711457180PD5930a3946144140PD5932a10060550320PD5934a11579611453PD5935a9671636335PD5936a2782282130PD5937a76097194368PD5942a5990384161PD5944a260930324PD5945a8833497434PD5946a3912312403PD5947a1779102151PD5948a151721052489PD5950a2190137229PD5951a3193215116PD5953a213653319PD5956a4085445692PD5959a2504128309PD5960a404527462PD5961a2314152104PD5964a15909269PD6016a21911951PD6041a17711522PD6042a7119274163PD6043a22764938217PD6044a257324461PD6045a233314132PD6046a2976281212PD6047a9442827142PD6048a3102257343PD6404a6553247139PD6405a35317628214PD6406a5026106185PD6409a8810183163PD6410a7313245194PD6411a6675147187PD6412a251872489182PD6413a4588157321PD6414a17611177PD6415a9545449363PD6416a333110072PD6417a1546134137PD6418a20202042PD6422a5181293362PD6466b180918061PD6684a13677663297PD6711a2191420721PD6719a4971153107PD6720a201820274PD6721a223113845PD6722a10110236196PD6727b6679410271PD6728b2578133113PD6729a24872372120PD6730b1008935697PD6731a2854913499PD6732b2915116178PD6733b467620293PD7066a3638122321PD7067a5980144226PD7069a5131146145PD7199a11308869PD7201a158414012PD7202a5141371452PD7203a156447177PD7204a217617544PD7205a7858208519PD7206a4740181127PD7207a28541676PD7209a16651361PD7210a13191031PD7211a8286544605PD7214a14937215PD7215a6384244259PD7217a9169381124PD7218a14741311PD7219a1162114570PD7220a270923139PD7221a20401069PD7238a221721946PD7240a5188261150PD7243a6774496203PD7248a13042613367PD7249a4584419181PD7250a7890430344PD7304a2003148154PD7305a4756309330PD7306a6863416410PD7307a8424135329PD7316a5647125188PD7321a6055488452PD7322a201521570PD7341a309084245PD7344a7223838PD7426a18497653485PD7428a15950694386PD8609a508745160PD8610a5098217142PD8611a6828230416PD8612a196814643PD8614a14397717PD8615a427012177PD8617a189918159PD8618a15061328PD8619a3571219248PD8620a26571412PD8621a8062873271PD8622a180934849PD8623a202029529PD8652a215856476387PD8660a226128672591PD8828a20616112PD8830a8246324129PD8832a264091512377PD8964a11151976247PD8965a4451449105PD8969a6820492126PD8973a590814983PD8977a404642732PD8978a6670876133PD8979a4037210742PD8980a15459803544PD8981a1748171172PD8982a21557690511PD8984a9152368163PD8995a7586634117PD8996a3230434201PD8997a2831159338PD8998a47696895PD8999a134713885PD9000a9510727208PD9001a270528938PD9002a8476916159PD9004a10625564284PD9009a1521025494PD9063a5004523385PD9064a12351769428PD9065a221015429PD9067a1554929PD9193a168278306PD9464a5251332349PD9467a246316133PD9539a3580233223PD9541a270618443PD9544a13891213PD9567a3512164118PD9568a303951259215PD9569a214113963PD9570a1406802PD9571a4700318315PD9572a408312917PD9573a161615940PD9574a163410221PD9575a650059197PD9576a178381007511PD9577a162416160PD9578a1088542PD9579a16345347PD9581a16162540PD9582a274099245PD9584a2753177146PD9585a10284865533PD9589a14139116PD9591a12966915PD9592a8496412228PD9593a161711323PD9595a9722626223PD9597a29114714PD9599a3295272131PD9600a201911438PD9604a106694035119PD9605a337325561PD9606a12221070PD9694a17126550PD9696a5865127332PD9702a7861395470PD9752a3476178293PD9754a189720346PD9755a171013858PD9756a421216752PD9759a219215054PD9760a5006209141PD9761a21031632PD9842a32012151PD9843a20101080PD9844a507800PD9845a314720829PD9847a22291334Grand Total 3479652 371993 77695 Table 3 gene_name n_syn n_mis n_non n_splice wMIS3 wNON3 wSPLICE3 qMIS3 qNON3 qSPLICE3 qALL3 TP5342637032123.409217548.572852386.1261910000CDH121219113.67105513127.588633101.5203810.0404397304.00E-140MAP3K14191902.585475538.779043800.07882551010PTEN115959.4277980288.766582376.47747991.24E-051.97E-115.58E-060MAP2K40196412.914165368.249519350.02174281.49E-074.67E-070.000559250CBFB2164817.760309871.0968958164.8823812.21E-094.35E-053.04E-120PIK3CA33860074.1273212000110AKT11360019.5479087000110RB1281252.0307281636.453085222.45146580.204726831.06E-100.00133772.67E-14NCOR13131731.4399990423.8813019.351056260.204726831.10E-110.34816571.48E-12MLL310372631.3670388512.15580354.295173280.204726832.82E-1211.56E-12CTCF417524.4832375523.853458522.21359630.002370530.000344140.249531431.99E-08ARID1A211901.7141836921.885768100.204726831.74E-0611.46E-05MED2308621.8321362319.809068410.9004860.204726830.000344140.804561045.60E-05FOXA1220107.8463216513.014858701.04E-050.676428415.78E-05TBX3210412.691549533.776552314.47697940.163063280.0007180119.24E-05CDKN1B02403.0891953194.249040900.204726832.11E-0510.00010703NF1112621.6769541512.98922636.546415090.204726830.0022270210.00065812CASP809305.6399445425.698451200.016392420.0129552910.00066763BRCA2011711.4742803213.23946147.992589570.204726830.0009150810.00070737SF3B1227105.43215542.9425743509.96E-05110.0013107GATA3612213.5003499813.651311315.17454660.035674950.2281306910.0023884FOXP113231.101550549.4167469821.84353910.206617470.347603380.058157450.00427114BRCA1110321.938998918.6772262315.82861070.204726830.21224730.402276590.00579244SPEN7131000.823039689.50219676010.0001282410.00611285RUNX138122.932887557.4164908826.083420.1537710.750852880.229547590.00889968ERBB2323005.0021794000.00041745110.01212771MLLT409501.8071610214.067407900.204726830.0055405410.01430864KDM6A15231.140239985.5324295716.58979280.204726830.617339260.120998360.01451691HIST1H3B37106.5286626223.735828300.012935970.4756805310.01457274TBL1XR125122.149130557.3826103415.13823620.204726830.738005130.402276590.04077154PTPRD321412.057190416.074649022.622532450.180054260.2133123310.05574899PRRX117105.2121310413.626266400.036524540.6286130610.08611263ZFHX3511700.859836878.91210596010.0033786710.09726602FBXW708203.4156887910.335630700.117843110.3220716210.10261303C11orf30113203.254413136.7716660200.069692070.5073292910.10939934KRAS06009.13712049000.00716467110.11016706STK1102201.5324171237.772097800.216766520.0476029410.15403046PREX2327103.078104241.9703871900.02044305110.16753773ATM117312.081411624.774136512.778550730.204535810.4756805310.17134935ARNT05202.3745419514.565876900.204726830.2141414110.20541186ERBB3116004.20153426000.01557192110.20541186UNC13C616601.060073114.940599100.204726830.1154822910.21415908ADAM29211202.526741227.0890182400.1537710.4756805310.21415908NTRK1112004.78083356000.01625294110.21415908JAK114211.019987189.568355316.245278880.206728690.3512869910.2159993USP605211.392664387.702047016.831808690.204726830.4756805310.2159993COL2A104031.02792734011.86629580.2047268310.249531430.2159993GRB709005.63291284000.01695079110.22126512LIFR14301.065223919.7724059100.204726830.1559264910.22739029PHF605104.136495167.8251962100.117843110.6827201610.22739029PIK3R1110013.1930056809.238671340.10284024110.22739029SMAD403201.625835516.586255800.204726830.2034367110.24860092SETD2211401.287643935.9399469300.204726830.2141414110.26855769MLH105112.189612377.007050527.554441520.204726830.7508528810.26855769AXL011004.78808167000.02301607110.26855769EIF1AX02103.4641943730.535005900.204726830.3741913310.28380774FLI127013.1216072013.12628570.153771110.28380774RHOA15007.26421487000.02590215110.28592545BCL2L201011.687830890119.5605740.2067286910.34816570.28592545PRKAR1A31300.4914522518.6842305010.0245286210.29117581EPS1504201.6647365713.480816900.204726830.2375032110.29216296FGFR2112004.13308918000.02726226110.29438728MLLT1019202.421976825.7172236800.195652540.5675345810.30074836PRKCG310102.969292396.7847110200.122418750.7729845410.30074836PMS109103.211882864.8382038700.117843110.8315191610.30376051AKT313201.2596178911.653917200.204726830.2698499310.31767708NIN211211.655745533.596771115.638633030.204726830.7447012810.31767708NF213111.460869897.192696789.34866140.204726830.7447012810.31767708EIF4A215013.02589708011.34481320.18005426110.31767708ETV505013.04974655013.92034810.19565254110.31767708MAP3K1327111.769140093.3960831410.69380680.20472683110.31767708HSP90AA114201.4459220311.822776300.204726830.2771321110.3435939CDKN2A02102.6707450240.549403800.204726830.3381374310.34771013IL7R05103.3728766910.317074800.187465980.6827201610.34771013CHEK208004.67537773000.03795388110.34771013GRIN2A115102.843617054.0928985800.11784311110.36072142STAG248301.148532215.6986282500.204726830.3381374310.37104828ROS1314211.714920443.491031893.086979030.204726830.7607056910.37104828IL6ST08103.040073925.0557550600.1537710.8315191610.37104828FAS03012.74746074017.93216360.20472683110.37104828SOX906103.1506497111.088437600.204535810.6827201610.37652905ATP1A104111.342010016.223498718.50093750.204726830.8075942610.37652905JAK206201.673652837.6142836300.204726830.4756805310.39240665TPM305005.57768864000.05366873110.42694914SMAD215102.915773276.3637513500.195652540.7447012810.43193114PDE4DIP216112.159740241.613307863.216562560.19565254110.43644694FANCD217201.726495337.1703133600.204726830.4756805310.44351306AURKA04102.79935478.3969386300.204726830.694360210.45063262PALB216201.510170537.4257244600.204726830.4756805310.45932694ATP2B3215003.26822605000.0619751110.45932694ROBO1312021.5188853206.787742110.20472683110.47297386CACNA1D316201.926610364.2786083400.204726830.7110104910.47463194SSX101101.3970926727.709011500.204726830.431521510.47646861ATRX216111.786999621.384053734.025986760.20472683110.47646861CHD1L07102.638029185.5371443800.204535810.8135323210.52315235EWSR137102.326018234.7589712500.204535810.8409464210.52988202SMAD303102.3351900916.965570700.204726830.5675345810.54163533CASC5110201.643939564.8579815300.204726830.676428410.54399602MYB06102.569468195.8057279400.204726830.8075942610.55313016ARID1B111201.745674935.6738749700.204726830.6286130610.56526095SET01101.0301517.437784900.204726830.5391049310.56636268NFE2L204102.252102948.2554580600.204726830.7110104910.56636268MYH11411021.3987396406.496866460.20472683110.5946251PTPRJ08102.406984115.6041942700.204726830.8315191610.59856783MAPK913011.88804069012.47507840.20472683110.59856783BCOR410111.289133522.348969298.179868160.20472683110.59856783DCUN1D101101.0596885612.103955100.204726830.6177296910.61434745SMC318012.0323238605.112945120.20472683110.61434745STAT5B15012.07343611010.05431310.20472683110.62494518FCGR2B12101.7096213816.752016700.204726830.5675345810.62820373IDH124101.932273388.173712900.204726830.7203447210.63344113KIT07012.212226506.682349480.20472683110.63344113PSIP114011.7839218508.628961470.20472683110.63344113DNMT3A28102.137736085.2482937100.204726830.8545606110.65605864CREBBP19201.531660114.9806582100.204726830.676428410.66524218LCK35102.08583717.3978295200.204726830.7447012810.66524218RAD2118003.16782164000.11784311110.66524218NOTCH2811410.738921164.848609092.5265866610.2913312610.67059674EPHA346201.166771585.2736226900.204726830.6286130610.67773946RPS6KB123011.401991011.01390430.20472683110.67773946ARID2210201.538182883.6778321100.204726830.7436666410.68859793NCKIPSD03011.51198597014.50843180.20472683110.68859793AKT213101.5800208612.971483500.204726830.6737511910.70126771NCOA239201.300329934.4226368600.204726830.6827201610.70126771STAT437102.074189663.640462300.204726830.9878810210.70126771ARAF36011.8763443107.214404040.20472683110.70295601TTL02101.6190348511.761437800.204726830.676428410.71190429TPR321002.20239869000.14421919110.72861369USP9X213201.500546243.1074415700.204726830.8135323210.72949689PRDM148101.920466895.2039935600.204726830.87122710.72949689CBLB212002.57831368000.14465511110.72949689PLCG137111.233009462.790660073.964851290.20472683110.72949689FNBP102011.06187844010.82243030.20472683110.72949689SETBP124110.621137452.9103640734.61937071110.72949689NTRK217101.9793985.4718329100.204726830.8431654810.73045244SKP213101.731017938.2698104200.204726830.7203447210.73713626INHBA32200.7405921215.2048904010.2133123310.74340443MYOC03101.782385558.0292552800.204726830.7303858410.74340443LASP104004.67269139000.153771110.74340443MAP3K454400.39717135.70381124010.2141414110.74444973CUX144300.595711727.44145638010.2375032110.74444973AFF358201.069686974.5629278500.216766520.6827201610.74444973LZTR101110.4301489110.22348329.4074402810.694360210.74444973CREB3L203101.770830638.9799114500.204726830.7110104910.74444973CCNE123101.446468958.2336109700.204726830.7274307610.74444973ATIC13101.313274118.2644714400.204726830.7303858410.74444973EP30029201.289247963.6025591600.204726830.7447012810.74444973TGFBR224101.392240957.8720342500.204726830.7447012810.74444973EXT104101.644674136.8861744800.204726830.7607056910.74444973GNAS16101.610459816.6061038700.204726830.8022662210.74444973DDX3X24101.213848095.3585717200.204726830.8135323210.74444973BCL907101.840626234.9877211800.204726830.8732154210.74444973IL21R06003.52075575000.153771110.74444973WSB105003.4859859000.153771110.74444973RSPO204003.79848364000.153771110.74444973EXT208003.10606888000.153771110.74444973ERG27003.0305369000.153771110.74444973CEP7606003.10681624000.15819813110.74444973ACVR2A17002.8880028000.15819813110.74444973NCOA3010002.65033842000.15819813110.74444973ETV134011.1558489806.744406440.20472683110.74444973PTPRC412101.814044852.2761603600.20472683110.74444973TRIP1128011.1571399906.645728930.20472683110.74444973WHSC1L107101.887200693.4486657800.20472683110.74444973ACSL603011.3526053408.253580520.20472683110.74444973MED12519101.864581671.5172530300.20472683110.74444973ROBO2112101.953642312.3098554600.20472683110.74444973TRRAP218102.070691812.0417366600.20472683110.74444973KEAP102101.1108848510.020832900.226244340.694360210.75763727GAS713101.394855128.1449802700.206617470.7380051310.75763727EPAS114101.440740437.2404578700.204726830.7607056910.77222715EZH213101.036971565.4279324900.204726830.8135323210.77222715CHIC203004.80823004000.17200778110.77222715NUP9819101.778816262.9393320600.20472683110.77222715FCRL424101.572899885.2874146200.204726830.8312231110.77626485EML404101.416490124.3521556200.204726830.8732154210.77626485MSH215101.588464744.0644565100.204726830.9298181210.77626485BRIP137011.2440203305.100980580.20472683110.77626485CDK12310101.753968472.4640631200.20472683110.77626485ZMYM206101.570892962.9525122200.20472683110.78018764TRAF713011.3837613808.091244830.21918258110.79181216ATR412111.142639561.30220852.528966920.20472683110.81031132ESR117002.89076417000.18962835110.81138156ABL227101.64350283.4280639500.20472683110.81138156PPM1D13101.269024365.3783006200.204726830.8135323210.81675904AR26101.646487064.7196390200.204726830.9173522310.81847467IKBKB14101.552911014.6764083900.204726830.8732154210.82146439PTPN13311201.139021692.6589248600.204726830.9068830110.82552546NUMA1110101.751289812.500424400.20472683110.82552546NTRK325011.28639506.311607710.20672869110.82552546MAP3K613200.7856588111.1605344010.3162761610.84351041MAP3K712110.751895085.525270977.4198048110.8135323210.86212037MLL49310.732215533.348903984.557796810.6827201610.86975173RABEP102200.812764819.56907507010.3381374310.8844798FGFR453200.712377319.812343010.3381374310.8844798CIC27101.354309094.4619214200.204726830.9659539310.8844798BRAF14101.346940253.8361639700.204726830.9659539310.8844798THRAP307002.42352468000.20453581110.8844798ATF103003.63137964000.20453581110.8844798RAB2513003.97209378000.20453581110.8844798TSC119002.36825858000.20453581110.8844798SPRED105002.69303714000.20453581110.8844798GATA125002.98270909000.20472683110.8844798TSC228101.532413794.2237836500.20472683110.8844798PTPRS05011.1460618906.910950820.22624434110.8844798ZNF21748101.471229823.3352388900.20472683110.89217818GRM3712101.58257472.391027800.20472683110.89527903NOTCH4412101.560205792.4428147400.20472683110.89527903BCL11A35101.081471775.5377451400.221060770.8522487610.90373276SMARCA468210.970272834.876889333.2577026410.676428410.91377736PIK3C2B39101.491000253.0261529700.20472683110.91377736NUP21438011.2252139104.251004760.20472683110.91907483STAT316002.62876566000.20472683110.91907483MDM225002.3417939000.20472683110.92791035CNOT306002.67099463000.20472683110.93086038COL1A138011.3766561502.749018230.20472683110.93086038HLF14002.92013347000.20472683110.93086038RPL1013003.01378253000.20472683110.93086038EPHB1811011.2546680303.943789130.20472683110.93086038WIF104002.97782629000.20472683110.93086038LRIG315101.154360023.6806510500.20544691110.93865644AFF446101.109836462.4346606700.20472683110.96051349SMC1A26101.168149282.8088456900.20472683110.96051349HOXC1301100.8787472923.8449957010.4756805311DDIT30010019.9559932010.4756805311JUN01100.8757985321.3973124010.5073292911NGFR01100.7417315717.7049839010.5675345811HNRNPA2B101100.8749458315.5435859010.5675345811TRIM2423200.676245885.85550565010.5675345811PPP6C01100.9575849214.7033778010.5889556211ALK31200.141260765.49290293010.6286130611PAX811100.6073935811.770135010.676428411NOV1010011.2462981010.676428411PTPRK23200.481749464.76014934010.676428411PICALM01100.5309926910.6466901010.6827201611MECOM44200.566229454.6132961010.6827201611RNF213714300.869927523.3741188010.6827201611MAPK801100.622106868.92295876010.694360211FLCN11100.499928639.95910664010.694360211C2orf4402100.9896418.81809012010.7110104911MYH969210.985853334.17610222.7275963110.7203447211PCM125200.701655113.66492225010.7380051311EBF122100.654902367.78522783010.7447012811WAS22100.891300076.70821643010.7607056911ARHGEF1244200.527954983.34585548010.7607056911ELF421100.373022946.91749603010.7609352311RASAL112100.704335316.8711391010.7609352311BAG421100.521689315.79912226010.7609352311ZNF33111100.470777835.15247363010.8135323211MKL122100.638541445.80304947010.8295531711PMS213100.972045224.4632183010.9068830111ECT2L13100.922853214.28852689010.9298181211TRIM3313100.844532964.14355159010.9541661711BCR23100.596771724.36832747010.9892520411PIK3C2A17001.37885191000.20472683111GAB204001.8638869000.20472683111GOPC04002.44975255000.20472683111SNX2915001.55128901000.20472683111ELN35001.87158294000.20472683111RAD5112001.6507903000.20472683111PIK3CB17001.91616143000.20472683111SMARCD102001.28492239000.20472683111TFE334001.32993783000.20472683111BCL303002.06236742000.20472683111TFRC13001.2684809000.20472683111NT5C202001.22507772000.20472683111MAP2K703002.14662606000.20472683111ERC125001.08097272000.20472683111XPO125001.22029739000.20472683111NCOA126001.13803848000.20472683111FUS03001.83145807000.20472683111FH03001.64479168000.20472683111CRKL12001.74042756000.20472683111SOX1013001.81438532000.20472683111DICER109001.67527459000.20472683111TCL1A01002.08373392000.20472683111CCNB1IP101001.01812531000.20472683111CHD8411001.01453315000.20472683111BIRC703003.22514884000.20472683111ARFRP102003.18228699000.20472683111FLT116001.30033175000.20472683111NBN03001.32738611000.20472683111UBR5615101.050586580.905367600.20472683111DYRK1B03001.45112962000.20472683111TFPT01001.03779242000.20472683111JAK326001.53208284000.20472683111ELL0400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119001.62166113000.20472683111PAK103001.65993377000.20472683111MSI203002.69606881000.20472683111GNAQ02001.39348912000.20472683111CREB3L113001.81076134000.20472683111SLC34A215001.92438902000.20472683111SLC45A324001.89426429000.20472683111TGM715002.06130059000.20472683111U2AF101001.01134263000.20472683111IKZF312001.01359241000.20472683111DDR238002.01982589000.20472683111H3F3A22002.76676186000.20472683111ERCC315001.92480778000.20472683111PRKCI02001.01493384000.20472683111GMPS03001.42945175000.20472683111RPN113001.4199228000.20472683111BAP115002.0622479000.20472683111PBRM106001.4764561000.20472683111RICTOR510001.11612985000.20472683111COX6C01003.05953848000.20472683111YWHAZ12002.15553021000.20472683111PIGA14002.10690303000.20472683111TSHR16002.21987591000.20472683111YWHAB01001.23608564000.20472683111KLK212001.9290159000.20472683111HOOK303001.30179344000.20472683111MAP2K103002.62242965000.20472683111MN106001.77106112000.20472683111CNBP11001.34129603000.20472683111AFF136001.10468163000.20472683111HRAS12002.63260136000.20472683111ERCC417002.14619413000.20472683111ERBB4411001.25154629000.20472683111SUZ1204001.80533192000.20472683111GPC536001.54031955000.20472683111IDH213001.80829649000.20472683111FAM46C13001.82843548000.20472683111FOXO425002.12001952000.20472683111Sep-0503002.44475487000.20472683111MUC102001.58747332000.20472683111PBX103001.834101000.20472683111TCEA112001.59127438000.20472683111FANCA18002.0480114000.20472683111NACA14001.574128000.20472683111LPAR113001.77913728000.20472683111CARD1149001.4829135000.20472683111CTNND125001.16048291000.20472683111MDM423001.45701523000.20472683111SMURF104001.86726236000.20472683111MTOR615101.271181951.3713111600.20472683111SSX401001.37669596000.20472683111RANBP1729001.93846614000.20472683111ZBTB1037001.66692169000.20472683111NRAS02003.12082935000.20472683111FANCG13001.51670963000.20472683111ITGB314001.55202368000.20472683111TNFAIP355001.10912008000.20510127111YAP102001.24536059000.20510127111MAML235101.077853112.2238793300.20537274111MAP3K302001.01169131000.20537274111MYCL102001.51584822000.20544691111PPARG12001.07455934000.20544691111PRCC02001.47609462000.20544691111MLL2820111.025916390.791147852.504879850.20544691111PTPRB914201.000690452.1499147200.20661747111SH3GL102001.77157082000.20661747111TPM401001.02019166000.20661747111FHIT01001.21734057000.20661747111MAP3K904001.24006062000.20672869111KDR47001.00233471000.20672869111YWHAQ01001.27435445000.2093365111FANCF02001.1397000.21012998111NFKB203001.2671814000.21047216111ZNF38412001.13915676000.21047216111VTI1A01001.1832564000.21047216111GRB211001.26997017000.21148356111CALR22001.08546268000.21177317111FOXO303001.35951653000.21330744111HIP124001.05443687000.21401794111CRTC302001.18775967000.21448992111PDGFB01001.15699376000.2149146111U2AF202001.29373004000.21676652111PDGFRB14001.16291973000.21676652111KIAA154938001.16230175000.21676652111RAC101001.41571317000.21676652111IGF1R37101.166736143.3952993600.21676652111MRAS01001.35023238000.21676652111PAX512001.19452276000.21676652111TRIM2702001.09755081000.21676652111SYK23001.03707885000.21695009111AXIN203001.05454289000.21762707111GATA202001.44384046000.21771126111MCL112001.50318682000.21918258111LHFP01001.28944601000.21918258111AXIN113001.06758587000.219265111RHOH11001.39130707000.22078719111CD79B11001.08651441000.22106077111CD7401001.17932934000.22106077111HEY122001.2257582000.22523613111LYL101001.11152141000.22617735111SMO13001.10305151000.22624434111VHL01001.2965381000.22624434111TAL112001.31708904000.22624434111SOX202001.17286825000.22786021111LMO201001.1417039000.22821956111FADD01001.32097679000.22845649111MYC22001.01201362000.23350724111TNFRSF1401001.16911065000.24033568111CANT122001.15670588000.24337128111FOXL202001.42654966000.24514993111MAP2K232001.05139795000.24745362111BCL201001.04483791000.24745362111HOXD1112001.06248832000.25235805111PAX701000.54592498001111FYN31000.37250789001111MAP4K322000.54023598001111DDX11104000.46844279001111WWTR110000001111MRE11A13000.9672297001111BIRC301000.56367938001111FLT432100.355747053.9154218501111RRM2B01000.82095255001111HERPUD101000.90342086001111POU1F101000.89695254001111GOLGA502000.88678911001111KLF601000.98036368001111FGFR330000001111MAP4K444000.5949114001111TCF301000.55174918001111SDHA30000001111SMARCE101010.77700506017.73040651111KDM5A32000.27532831001111NOTCH375100.419640711.8775461401111PAK312000.89179386001111FGFR153000.63664631001111PIK3C314000.90211582001111HOXA901000.98759182001111TP7332010.6325160109.32780451111RUNX1T123000.75852992001111DNM233000.81508269001111TRPM369100.853889981.5653813901111CYLD12000.54261425001111GNA1111000.6943319001111EZR32000.73431655001111CDC611000.58206674001111HSP90AB132000.54801854001111ABL124010.99323909014.24060621111MAPK121000.62314354001111PATZ110000001111EEF1A211000.55527024001111PTK641000.40910022001111NDRG132000.96544826001111ERCC202000.93024085001111CD79A10000001111PPP2R1A11010.3762480908.976578741111CDK611000.73339956001111HOXA1321000.51815986001111MLLT643000.66713856001111RNF4302000.88389479001111DDX522010.82305172011.33256841111PHOX2B21000.65825919001111HSPA802000.98099208001111CCND101000.92384463001111BIRC220000001111CBL43000.69310234001111ELK321000.53627653001111SH2B302000.98626378001111ALDH210000001111RAB2310000001111E2F310000001111TFEB10000001111VEGFA10000001111RAD5002000.54142213001111ACVR111000.41081609001111RPL2210000001111TRIM6201000.62125812001111CCND210000001111CD27411000.8491144001111KCNJ501000.63919195001111HOXC1111000.8287603001111STIL23100.611197783.0893002501111Sep-0631000.43172096001111FOXA211000.44511267001111KDM5C47000.94834001111SBDS10000001111BCL11B22000.48501038001111TRAF201010.71167884020.69436221111HOXD1311000.55041374001111MYOD101000.69104551001111CBFA2T301000.5074803001111MLLT101000.58886425001111MNX101000.66894426001111BTG110000001111MEN112010.97081723021.260291111MYCN01000.40593584001111CDK411000.87054328001111NKX2-101000.59456398001111PIM111000.82345935001111MAP2K511010.6030613505.845388561111FBXO1103000.95549973001111NCOA401000.50186514001111NDST431000.18933331001111MAP3K1212010.72671743013.75639361111TCF1202000.81536295001111BCL2A110000001111PML21000.27622897001111GATA622000.70072179001111RPTOR46000.99183682001111BRD423000.62217729001111CBLC01000.76243989001111PRDM1634000.70051296001111IKBKE53000.76046468001111CXCR731000.47443424001111ARHGAP2602000.78992014001111RSPO301000.94896328001111MTDH22000.84538789001111NFIB22000.82601197001111TCF7L202000.99899763001111CHEK101000.63116992001111ARID5B44000.68195307001111FOXO101000.45678353001111JAZF110000001111CHD135000.57985051001111XPC22000.53410492001111BUB1B12000.62435575001111FANCC22000.80628498001111RALGDS02000.82997155001111PCSK722010.6795960409.205003841111SHC111000.51709229001111FUBP112000.89043778001111RBM1512000.52335221001111REL22000.72501986001111FEV10000001111TERT22000.45082189001111ZNF70430000001111WRN23000.48419197001111CDX211000.71579819001111NSD148100.788440771.3571917401111RET56000.95928189001111MAPK720000001111CTNNB123000.8565748001111SF131000.33433942001111LRP1B924300.808215141.5797558601111TET238100.959665691.5602879401111ZRSR211000.48940116001111ASPSCR101000.57190038001111BRD311000.39506356001111MAP3K221000.39787791001111KIF5B34100.924706542.8780199801111CHCHD710000001111ASXL134100.674590462.7663413801111BCL2L110000001111BPTF59010.7744725904.18905991111PLEKHG502000.72033819001111GPHN12000.57445945001111CAMTA145000.69205268001111MLLT311000.4269138001111MALT102000.88668132001111CLP110000001111TAF1512000.88265182001111MYD8820000001111MAP3K1140000001111PTPRM74010.3980239102.155964991111CHD224100.603423631.8791270801111DDX1011010.2841094207.229818971111AURKB01000.93715545001111PER155010.8244377704.94761031111PTPN1122000.82244229001111CIITA12000.56908912001111NRIP114000.98614666001111PRF141000.31989306001111NPM111000.81878198001111PLAG111000.50369898001111P2RY801000.77272498001111EP40076100.472451861.2718897501111TMPRSS211010.50500326010.74996831111SS18L110000001111C15orf5513000.87723562001111Sep-0912010.87463452012.35552631111FAM22A01000.46354378001111WT112000.85953984001111IKZF122000.81176875001111PTCH135000.83828001111IRS221000.19609213001111TAL210000001111MITF01000.53302954001111PTPRT58000.86852507001111SRGAP343100.513207753.163731701111NCOR279000.73279451001111IGF2R65100.453210921.6938523801111SRC20010010.11859271111BLM14000.97130112001111MAP3K543100.447232462.6426283401111HIST1H4I10000001111ZNF52132000.31364143001111TOP112010.7585308507.008332511111DAXX22000.65968819001111SDHD10000001111POU5F121000.69623669001111OLIG210000001111FGFR1OP01000.67245987001111CHUK02000.95827608001111CEBPA01000.67784151001111PIK3R202000.93515765001111KAT6A11000NANANANANANANASRSF31100NANANANANANANACNTRL1920NANANANANANANACCDC1703420NANANANANANANASPECC11401NANANANANANANAKAT6B61100NANANANANANANASRSF21410NANANANANANANANBPF1031810NANANANANANANARAD51B1100NANANANANANANAAMER161200NANANANANANANAFAM22B1200NANANANANANANAMDS20100NANANANANANANA Table 4 gene_ namen_ synn_ misn_ nonn_ splicenum_ indelsnum_ uniquewMIS3wNON3wSPLICE3wINDqMIS_ tieredqNON_ tieredqSPLICE_ tieredqIND_tieredgALL_ tieredknownCGTP53426370328577138.488624557.103224435.485088491.0789960001.86E-810TRUEMAP3K141919090852.795496836.4344360146.6495980.035247900.935447832.35E-490TRUECDH1212191145453.75225448117.8965104.178082130.9813420.02547274003.81 E-330TRUEPTEN11595292610.369027481.615293581.6601712163.2717411.27E-061.91E-112.81E-067.11E-260TRUEMAP2K401964171510.322066248.863363839.230474393.6199973.27E-071.82E-060.000902593.55E-140TRUEPIK3CA338600231976.1234250045.596355100.712999440.935447831.01E-110TRUECBFB216487719.540386775.6426793178.9881291.71959111.25E-102.77E-058.33E-135.78E-080TRUEAKT1136000020.031931200000.712999440.9354478310TRUERB12812511112.2090439433.77055823.169985129.42021930.152972437.96E-110.000902591.37E-060TRUEMLL3103726345411.4038654510.83959174.348164321.87276540.152972431.12E-110.935447836.78E-100TRUENCOR131317314141.3091392119.00024268.4607420914.72610960.152972436.61E-110.42009829.72E-050TRUETBX32104121212.439633828.043189813.003852574.26430560.152972430.001252270.935447836.98E-160TRUEGATA361221123823.5906766613.493307115.7733242484.0750940.024647710.27561310.935447834.05E-840TRUERUNX1381219173.268189847.6030950728.213684791.26361710.096580420.712999440.210702382.99E-150TRUEPIK3R11100119183.3707891509.7744262163.2991980.055978650.712999440.935447831.87E-133.76E-14TRUEARID1A2119016161.6422319619.2913706018.53476090.152972432.51E-060.935447835.39E-065.64E-11TRUECTCF41752335.2204390724.475187124.901437910.73924660.000249960.000255150.233178320.150503512.10E-10TRUECDKN1B0240553.0195089187.558331066.25726420.152972432.06E-050.995562592.14E-051.26E-09TRUEFOXA122010666.748794859.9288163034.0909511.46E-050.7129994419.72E-056.32E-09TRUEMED230862771.6374485515.26614989.3090539713.01638050.152972430.000832630.935447830.00560814.24E-07TRUENF11126212121.5812476910.31232676.0895375610.78173150.152972430.005052930.935447830.002167691.48E-06TRUESPEN71310014130.856977788.8832955609.537003440.152972430.000164580.935447830.003748241.56E-05TRUEZFP36L10310882.7808649422.1661308063.07538210.197685750.9282894213.81 E-053.92E-05FALSEHIST1H3B3710227.2983556725.3590889038.84155060.005173010.501547610.055503290.00023971TRUEMLLT40950771.5554476310.7826997010.88908390.152972430.012521940.935447830.012360440.000246TRUETBL1XR12512642.223112976.381230315.109910819.40924960.152972430.712999440.42009820.012360440.00027949TRUEBRCA201171661.3715511510.14651897.352028754.664531560.152972430.00234920.935447830.332581970.00037238TRUEBRCA111032551.902019147.0966419715.1287676.946598480.152972430.27561310.442848170.148951620.00064594TRUEXBP10200772.121908280068.4605560.197685750.9282894216.49E-050.00068641FALSEHLA-DRB12202751.64101588044.556940347.4805250.197685750.9282894210.01391350.00132798FALSESF3B122710005.705568912.64328888001.14E-050.712999440.9354478310.00175413TRUEFOXP11323221.02872997.7183649719.88544467.432860370.153613960.486638630.067266650.541791940.00257002TRUECASP80930005.6848103722.6341116000.008265650.01551570.9354478310.00334101TRUEMYB0610552.493896554.97250701016.71330010.152972430.712999440.935447830.007973630.004917TRUEERBB232300115.20498261002.024800998.21E-050.712999440.9354478310.01001401TRUEFBXW70820223.575009889.2394574407.319737160.069947470.354565990.935447830.545167350.02874291TRUESETD221140661.328138235.2049785506.205803720.152972430.27561310.935447830.148951620.03331321TRUECRIPAK2900754.106713240030.25960920.197685750.9282894210.083440530.04077807FALSEMEN11201331.03690891023.420898312.65657340.159542760.712999440.935447830.124481040.08141925TRUESMAD40320221.7023064814.573980209.2438060.152972430.234342980.935447830.439699850.08905229TRUEATM11731551.894335763.688992422.483650824.175337760.152972430.709276080.935447830.478198620.0902412TRUEERBB311600224.17075849003.794915950.007297290.712999440.935447830.990311350.11587142TRUEESR11700332.686170470013.13085610.152972430.712999440.935447830.117580480.1369056TRUEHSP90AB13200440.65045210014.31272890.152972430.712999440.935447830.03397390.15882784TRUENCOA3010002242.6632142007.291992340.12511930.712999440.935447830.187356130.17233662TRUESTK110220111.4513458432.668462405.87366840.159021190.058770970.9354478310.19619531TRUEDLG10822332.81558538.3122866811.03563028.092523660.197685750.92828942110.20376222FALSEZFHX351170330.796541047.4995055902.189648210.152972430.007610240.9495048810.20564876TRUENPAS421040003.9183485224.9580965000.197685750.36928655110.23982079FALSENLRP23633111.239107389.9097364826.17711892.470881360.197687460.92828942110.23982079FALSEHSP90AA11420221.5135778910.519725506.090239410.152972430.342539230.935447830.642438520.24055196TRUEFIP1L12400431.358090110012.48266630.152972430.712999440.935447830.124481040.26344225TRUEPSIP11401221.7518193508.000979289.38169410.152972430.712999440.935447830.439699850.29588875TRUEFOXO30300331.281700490012.01196830.157403610.7129994410.128265550.35248986TRUEEIF4A21501113.18697649011.6025336.129045280.133601950.712999440.9354478310.35248986TRUEC11orf3011320003.303384376.09408889000.037506570.615725990.9354478310.35390454TRUEMLL4931770.75139083.023142674.71292814.661049340.152972430.712999440.935447830.282850020.35696303TRUEMET0700441.82066829007.387527810.152972430.712999440.935447830.187356130.36010944TRUEPDGFB0100221.199593230020.80444380.153613960.718698020.935447830.146966790.36153822TRUEKCNB231120552.066911666.15905017014.83335710.197685750.9282894210.921555540.36445965FALSEKRAS0600008.903642740000.004983870.712999440.9354478310.37189496TRUEPRKAR1A3130110.4608014515.434249106.561915250.152972430.038740750.9354478310.39425118TRUEAFF35820331.052146574.0946486906.153647570.156198170.712999440.935447830.439699850.39425118TRUEPRRX11710004.7734119511.7874106000.037495490.712999440.9495048810.39425118TRUEUNC13C61660221.016257454.0574889602.347780730.152972430.234342980.9354478310.39827511TRUEHSPA80200330.915814430012.13678340.152972430.712999440.935447830.128265550.40485531TRUEAXL01100314.31725672002.834019550.021599050.712999440.9354478310.4176086TRUENF21311111.522043246.8585215110.16534954.197200410.152972430.712999440.9354478310.4176086TRUEPREX232710003.050659811.67564854000.011633250.712999440.9354478310.4176086TRUEMYH96921331.083184444.23819832.968745223.903937490.159021190.712999440.935447830.763982670.4176086TRUEATIC1310221.263436967.09233308.433364010.15312880.712999440.935447830.478198620.4176086TRUEPTPRD32141001.863231364.761945092.3226615200.152972430.342539230.9354478310.4176086TRUEKEAP10210221.042330428.7701729108.494697570.164198250.712999440.991498810.478198620.42226248TRUEZMYM20610331.56258172.5427536105.620632270.152972430.712999440.935447830.478198620.42226248TRUENOTCH441210441.548791242.2718703905.181334860.152972430.712999440.935447830.427442410.42226248TRUEIL7R0510113.133814038.1899755405.600100280.152972430.712999440.9354478310.42226248TRUECASC511020331.683018554.2051484903.365130910.152972430.712999440.935447830.89013810.42951487TRUEGRIN2A11510222.499762593.1652758303.621770280.128128690.712999440.935447830.998503740.4316877TRUELIFR1430111.019267597.9611280702.346769920.152972430.234342980.9354478310.4316877TRUENTRK111200004.797853740000.008184640.712999440.9354478310.44993119TRUEMAP3K132711111.84903943.091341811.11849662.697507890.152972430.712999440.9354478310.45781299TRUELZTR10111220.432958869.536188569.813046365.983275820.152972430.712999440.935447830.650570610.46963592TRUEIL6ST0810113.130837354.3743840402.812571860.103245970.712999440.9354478310.46963592TRUEEXT10410221.518778345.753340706.95546270.152972430.712999440.935447830.564173250.47445889TRUEARID1B11120331.578963234.7596782103.529271830.152972430.712999440.935447830.848948760.48129522TRUESET0110111.0667898414.943363708.579377130.152972430.644650980.935447830.95760520.48129522TRUEJAK11421220.948719517.788684315.568773784.413574310.153613960.50154760.935447830.89013810.48129522TRUERPL50100220.993649940016.78880170.152972430.712999440.935447830.187356130.48129522TRUEEWSR13710112.621763175.2737378703.77476750.133672760.712999440.9354478310.48881814TRUESOX101300221.870920250011.42717880.152972430.7129994410.332581970.50957773TRUETRA2B0503004.1997784045.656664900.197685750.928289420.9409149210.52328392FALSECACNA1 D31620222.012368293.9137046902.324089370.152972430.712999440.9354478310.53506929TRUECOL1A13801331.3574735402.802304665.000701170.152972430.712999440.935447830.554338030.54387325TRUEGRB70900005.367519980000.011633250.712999440.9354478310.54387325TRUENOTCH281141330.800949264.559915262.710987693.16251150.152972430.342539230.935447830.945596770.54903356TRUEBAG42110220.573918245.69615559011.48335170.152972430.712999440.935566560.332581970.55385901TRUEAURKA0410112.253558955.8159382906.328286690.152972430.712999440.9354478310.55385901TRUECREBBP1920331.463806334.288765603.210948980.152972430.712999440.935447830.931987360.56667723TRUEARNT0520002.2946424112.4951285000.152972430.27561310.9354478310.56937858TRUENIN21121111.677139523.136359475.88476931.247695160.152972430.712999440.9354478310.62089606TRUE Table 5 Chr Start End Gene Alternative_ Gene_name Gene_source / PMID Paper title 102703552227149959ABI1Cancer_Gene_Census9133589333133763062ABL1Cancer_Gene_Census1179068462179198819ABL2Cancer_Gene_Census2223725652223809357ACSL3Cancer_Gene_Census5131142683131347936ACSL6FACL6Cancer_Gene_Census2158592958158732374ACVR1ACVR1 / ALK2Cancer_Gene_Census2148602086148688393ACVR2ACancer_Related_Genes_Pane I193620892136229779AD000671.3MLL4PMID: 24292195Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups.4175750819175899331ADAM29Cancer_Related_Genes_Pane IMutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing.48785615488062190AFF1M LLT2Cancer_Gene_Census2100163718100759201AFF3LAF4Cancer_Gene_Census5132211071132299326AFF4AF5q31Cancer_Gene_Census79157018191739989AKAP9Cancer_Gene_Census14105235689105262080AKT1Cancer_Gene_Census194073622440791302AKT2Cancer_Gene_Census1243651535244013430AKT3Cancer_Related_Genes_Pane I12112204346112247782ALDH2Cancer_Gene_Census22941564030144432ALKCancer_Gene_Census5112043195112181936APCCancer_Gene_CensusX6676446566950461ARCancer_Related_Genes_Pane IX4742051647431319ARAFCancer_Related_Genes_Pane I206232999662339355ARFRP1Cancer_Related_Genes_Pane I5142149949142608576ARHGAP26GRAFCancer_Gene_Census11120207946120360645ARHGEF12Cancer_Gene_Census12702252227108601ARID1ACancer_Gene_Census6157099063157530401ARID1BCancer_Gene_Census124612349246301823ARID2Cancer_Gene_Census106366105963856703ARID5BPMID: 23636398Integrated genomic characterization of endometrial carcinoma.1150782181150849244ARNTCancer_Gene_Census177993542679975280ASPSCR1Cancer_Gene_Census203094615331027122ASXL1Cancer_Gene_Census125115781951214907ATF1Cancer_Gene_Census2216176540216214487ATICCancer_Gene_Census11108093559108239826ATMCancer_Gene_Census1116915290116952883ATP1A1Cancer_Gene_CensusX152783134152848397ATP2B3Cancer_Gene_Census3142168077142297668ATRCancer_Gene_CensusX7676035977041719ATRXCancer_Gene_Census205494444554967393AURKACancer_Related_Genes_Pane I1781080518113936AURKBCancer_Related_Genes_Pane I16337440402673AXIN1Cancer Gene Census176352468563557765AXIN2Cancer Gene Census194172510841767670AXLCancer_Related_Genes_Pane IMutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-qeneration DNA sequencing.83803431238070809BAG4Cancer_Related_Genes_Pane 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diagnosis using next-generation DNA sequencing.11113930315114121395ZBTB16ZNF145Cancer_Gene_Census167281678473082274ZFHX3Cancer_Related_Genes_Pane lMutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing.146925437569261453ZFP36L1Idenified from this analysis132053281020663253ZMYM2ZNF198Cancer_Gene_CensusX7045947470474996ZMYM3PMID: 24014293Recurrent gene mutations in CLL.205218360452226446ZNF217Cancer_Related_Genes_Pane l195402423554083523ZNF331Cancer_Gene_Census1267756436798676ZN F384Cancer_Gene_Census182264188822932214ZNF521Cancer_Gene_Census3179040779179053323ZNF639Cancer_Related_Genes_Pane lMutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing.88155076981787016ZNF704Cancer_Related_Genes_Pane lMutation detection in formalin-fixed prostate cancer biopsies taken at the time of diagnosis using next-generation DNA sequencing.X1580859515841383ZRSR2Cancer_Gene_Census Table 7A Sample Normal VariantlD Chr om Position Reference Mutant Gene Transcript RNA CDS Protein Type Effect Propor tion_ Mutant _Reads _Subs Propor tion _Mutant _Reads _Indels PD11389aPD11389b124950758214105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.38.PD9845aPD9845b131054444314105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.37.PD8977aPD8977b132228477214105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.49.PD4248aPD4248b151591198014105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.32.PD14453aPD14453b153535146414105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.45.PD6043aPD6043b209998005514105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.79.PD9572aPD9572b226365322514105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.46.PD14462aPD14462b230774726914105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.3.PD8609aPD8609b240946148214105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.15.PD22364aPD22364b241691023414105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.72.PD11765aPD11765b244047838314105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.21.PD13428aPD13428b246550710514105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.7.PD17973aPD17973b.14105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.19.PD24216aPD24216b.14105246551CTAKT1CCDS9994.1r.603g>ac.49G>Ap.E17KSubmissense0.56.PD9541aPD9541b12858212171940762959CTAKT2CCDS12552.1r.348a>ac.49G>Ap.E17KSubmissense0.36.PD11365aPD11365b18150220025112176063CCAAPCCCDS4107.1r.5152 5153insac.4772 4773insAp.P1594fs*38Insframeshift.0.24637681PD9065aPD9065b1527958236127023430CARID1ACCDS285.1r.908_917del UGGCCUGGCAc.537_546del TGGCCTGGCAp.G180fs*49Delframeshift.0.5483871PD14467aPD14467b2039379320127023615TARID1ACCDS285.1r.1093_1118del26c.722_747del26pS241fs*1Delframeshift.0.23076923PD9760aPD9760b1700212597127024001CCGARID1ACCDS285.1r.1478 1479insgc.1107_1108insGp.Q372fs*28Insframeshift.0.34090909PD9063aPD9063b2544623933127057835CTARID1ACCDS285.1r.1914c>uc.1543C>Tp.Q515*Subnonsense0.2.PD7322aPD7322b2567881031127057894CAARID1ACCDS285.1r.1973c>ac.1602C>Ap.Y534*Subnonsense0.34.PD11375aPD11375b1703601437127059206GCGARID1ACCDS285.1r.2215delCc.1844delCp.S617fs*2Delframeshift.0.18421053PD4613aPD4613b2261697944127087360CGARID1ACCDS285.1r.2305c>gc.1934C>Gp.S645*Subnonsense0.38.PD17981aPD17981b2423660516127087892CARID1ACCDS285.1r.2551 2566del16c.2180_2195del16p.P728fs*9Delframeshift.0.35294118PD5937aPD5937b1587037155127088658AACARID1ACCDS285.1r.2638 2639inscc.2267 2268insCp.Q758fs*59Insframeshift.0.13414634PD11402aPD11402b1693009608127094454CCTARID1ACCDS285.1r.3533 3534insuc.3162 3163insTp.Y1055fs*50Insframeshift.0.51515152PD5937aPD5937b1587037159127097621CACARID1ACCDS285.1r.3582delAc.3211delAp.K1072fs*21Delframeshift.0.23214286PD11399aPD11399b1595947145127100181CGCACARID1ACCDS285.1r.4349 4351delGCAc.3978 3980delGCAp.Q1334delQDelinframe.0.10638298PD7250aPD7250b1588907132127105738AARID1ACCDS285.1r.5721_5734del AAUGAUGAGGAGAUc.5350_5363del AATGATGAGGAGATp.N1784fs*13Delframeshift.0.26666667PD11381aPD11381b1718184086127105930TTGARID1ACCDS285.1r.5912_5913insgc.5541 5542insGp.D1850fs*4Insframeshift.0.3PD11397aPD11397b1289137706127106354CTARID1ACCDS285.1r.6336c>uc.5965C>Tp.R1989*Subnonsense0.65.PD7206aPD7206b2414633885127106504CTARID1ACCDS285.1r.6486c>uc.6115C>Tp.Q2039*Subnonsense0.11.PD14441aPD14441b1812025755127106921GAGARID1ACCDS285.1r.6904delAc.6533delAp.D2178fs*22Delframeshift.0.18181818PD23579aPD23579b23848561866157405953CCGARID1BCCDS5251.1r.2134_2135insgc.1982 1983insGp.S665fs*27Insframeshift.0.25925926PD9063aPD9063b25448191166157502130GTARID1BCCDS5251.1r.3261g>uc.3109G>Tp.E1037*Subnonsense0.28.PD4252aPD4252b18467117536157505463CGARID1BCCDS5251.1r.3542c>ac.3390C>Gp.Y1130*Subnonsense0.49.PD4844aPD4844b3.6157527960GCGARID1BCCDS5251.1c.5632delCp.Q1879fs*77DelFrameshift del.0.23333333PD10011aPD10011b23059314202031022380TGCAGTASXL1CCDS13201.1r.2290_2293del GCAGc.1866_1869del GCAGp.Q623fs*79Delframeshift.0.22916667PD5937aPD5937b125043749611108170464GTATMCCDS31669.1r.5414a>uc.5029G>Tp.E1677*Subnonsense0.28.PD4198aPD4198b254434856311108216545CTATMCCDS31669.1r.8879c>uc.8494C>Tp.R2832CSubmissense0.24.PD14457aPD14457b18404063353142215210CTATRCCDS3124.1r.6013g>ac.5891G>Ap.W1964*Subnonsense0.17.PD23564aPD23564b23375962063142217556CTCATRCCDS3124.1r.5562delAc.5440delAp. R1814fs*10Delframeshift.0.14893617PD5956aPD5956b16063839983142280229ATAATRCCDS3124.1r.1326delAc.1204delAp.M402fs*37Delframeshift.0.50793651PD18749aPD18749b2433909743X76776358GAATRXCCDS14434.1r.7323c>uc.7108C>Tp.Q2370*Subnonsense0.31.PD11462aPD11462b2187347238X76776395CAATRXCCDS14434.1r.7287-1a>uc.7072-1G>Tp.?Subess splice0.16.PD5937aPD5937b158736040016348179CCGAXIN1CCDS10405.1r.1698 1699inscc.1326 1327insCp.A443fs*26Insframeshift.0.14285714PD6412aPD6412b225860491216396589CTAXIN1CCDS10405.1r.809g>ac.437G>Ap.R146QSubmissense0.58.PD4958aPD4958b2490564834X39916576TABCORCCDS48093.1r.4658-2a>uc.4429-2A>Tp.?Subess splice0.33.PD4109aPD4109b1822358072X39933958GTBCORCCDS48093.1r.870c>ac.641C>Ap.S214*Subnonsense0.12.PD24333aPD24333b25760402847140481411CTBRAFCCDS5863.1r.1458a>ac.1397G>Ap.G466ESubmissense0.42.PD11742aPD11742b23791870501741203096GBRCA1CCDS11453.1 r.5712_5713ins c.5315_5316insp.F1772fs*29Insframeshift.0.12PD7215aPD7215b22539126071741209130TABRCA1CCDS11453.1r.5613a>uc.5216A>Tp.D1739VSubmissense0.42.PD9585aPD9585b22734902281741234451GABRCA1CCDS11453.1r.4724c>uc.4327C>Tp.R1443*Subnonsense0.7.PD7067aPD7067b12265893731741246005CABRCA1CCDS11453.1r.1940g>uc.1543G>Tp.E515*Subnonsense0.16.PD23561aPD23561b24027408341741247864CCTBRCA1CCDS11453.1r.1065_1066insac.668 669insAp.A224fs*4Insframeshift.0.07352941PD13604aPD13604b22659838161332911530CGBRCA2CCDS9344.1r.3271c>gc.3038C>Gp.S1013*Subnonsense0.18.PD11372aPD11372b12131959451332913464CTBRCA2CCDS9344.1r.5205c>uc.4972C>Tp.Q1658*Subnonsense0.23.PD24191aPD24191b23890617901332914239ABRCA2CCDS9344.1r.5981 6840del860c.5748 6607del860p.H1918fs*20Delframeshift.0.25PD23565aPD23565b24173224651332914451CTBRCA2CCDS9344.1r.6192c>uc.5959C>Tp.Q1987*Subnonsense0.15.PD13604aPD13604b22659838171332914562CTBRCA2CCDS9344.1r.6303c>uc.6070C>Tp.Q2024*Subnonsense0.14.PD6042aPD6042b22563182901332914574GTBRCA2CCDS9344.1r.6315a>uc.6082G>Tp.E2028*Subnonsense0.26.PD24326aPD24326b25368783861332929050CTBRCA2CCDS9344.1r.7293c>uc.7060C>Tp.Q2354*Subnonsense0.37.PD9000aPD9000b17273671351332929199CAACBRCA2CCDS9344.1r.7443_7444del AAc.7210_7211del AAp. K2404fs*7Delframeshift.0.57575758PD8978aPD8978b15854547141332937614GBRCA2CCDS9344.1r.8509_8521 del UGGGCUCUCCUGAc.8276_8288del TGGGCTCTCCTGAp.G2760fs*13Delframeshift.0.73333333PD8984aPD8984b15443566121332954022CCABRCA2CCDS9344.1r.9322 9323insac.9089_9090insAp.T3033fs*11Insframeshift.0.18421053PD23579aPD23579b23842764731540477505ACABUB1BCCDS10053.1r.1087delCc.892delCp.M300fs*31Delframeshift.0.16981132PD4607aPD4607b22494696012202150003CTCASP8CCDS42798.1r.1640c>uc.1444C>Tp.Q482*Subnonsense0.24.PD7209aPD7209b22493015861667063312TCCBFBCCDS45508.1r.263u>cc.2T>Cp.M1TSubstart-lost0.5.PD7210aPD7210b22609243841667063389GCCBFBCCDS45508.1r.339+1a>cc.78+1G>Cp.?Subess splice0.39.PD13310aPD13310b12901693951667063672CTCBFBCCDS45508.1r.382c>uc.121C>Tp.Q41*Subnonsense0.83.PD18046aPD18046b21380296521667063709CACBFBCCDS45508.1r.419c>ac.158C>Ap.S53*Subnonsense0.57.PD9761aPD9761b13116350321667063717GTCBFBCCDS45508.1r.426+1g>uc.165+1G>Tp.?Subess splice0.38.PD13762aPD13762b15084761961667063717GTCBFBCCDS45508.1r.426+1g>uc.165+1G>Tp.?Subess splice0.38.PD17973aPD17973b18216251511667063717GACBFBCCDS45508.1r.426+1g>ac165+1 G>Ap.?Subess splice0.36.PD18047aPD18047b21119593421667063717GGTCBFBCCDS45508.1r.426+1 426+2insuc.165+1 165+2insTp.?Insess splice.0.4PD4982aPD4982b22624443181667063717GCCBFBCCDS45508.1r.426+1g>cc.165+1G>Cp.?Subess splice0.64.PD14458aPD14458b24635292101667063717GCCBFBCCDS45508.1r.426+1g>cc.165+1G>Cp.?Subess splice0.53.PD4972aPD4972b15721287391667070577GGTCBFBCCDS45508.1r.462 463insuc.201_202insTp. P70fs*13Insframeshift.0.2962963PD4976aPD4976b17370353871667070599GGGACBFBCCDS45508.1r.484_485insgac.223 224insGAp.Q77fs*13Insframeshift.0.625PD18269aPD18269b24473982261667070599GTCBFBCCDS45508.1r.484a>uc.223G>Tp.G75*Subnonsense0.39.PD7218aPD7218b16285634961667070611CACCBFBCCDS45508.1r.497delAc.236delAp.T80fs*9Delframeshift.0.5483871PD18756aPD18756b25373732491667116115GACBFBCCDS45508.1r.661-1a>ac.400-1G>Ap.?Subess splice0.3.PD6044aPD6044b17414498213105439049CTCCBLBCCDS2948.1r.1570delAc.1248delAp.G417fs*5Delframeshift.0.19178082PD18748aPD18748b17998408141668771311GCDH1CCDS10869.1r.185_192del GCCAGCCAc.1delAp.?Delstart-lost.0.2173913PD13763aPD13763b18180149341668771344CACDH1CCDS10869.1r.217c>ac.26C>Ap.S9*Subnonsense0.4.PD5961aPD5961b22514462111668772218CTCDH1CCDS10869.1r.258c>uc.67C>Tp.Q23*Subnonsense0.23.PD14472aPD14472b20426846051668772225CCGCDH1CCDS10869.1r.265_266insgc.74_75insGp.E26fs*8Insframeshift.0.48275862PD9067aPD9067b25496754371668772229GGCCDH1CCDS10869.1r.269 270inscc.78_79insCp.C28fs*6Insframeshift.0.21276596PD4194aPD4194b25658544571668772236CACCCCGTGCDH1CCDS10869.1r.277_280del ACCCinsgugc.86_89del ACCCinsGTGp.H29fs*27Complexframeshift.0.25PD14460aPD14460b22263967891668772259CTACACTGCDH1CCDS10869.1r.300_303del UACAinsuac.109_112del TACAinsTGp.Y37fs*21Complexframeshift.0.36842105PD9578aPD9578b25347867451668772314GGTGCDH1CCDS10869.1r.354+1 354+2delauc.163+1 163+2delatp.?Deless splice.0.19444444PD6016a2PD6016b13190920301668835613TACDH1CCDS10869.1r.395u>ac.204T>Ap.Y68*Subnonsense0.29.PD7204aPD7204b21785230921668835751CCACDH1CCDS10869.1r.533 534insac.342 343insAp.T115fs*53Insframeshift.0.36363636PD11376aPD11376b12548570501668842326GCCDH1CCDS10869.1r.579-1a>cc.388-1G>Cp.?Subess splice0.15.PD13306aPD13306b15603757571668842348GCGCDH1CCDS10869.1r.601delCc.410delCp.A137fs*78Delframeshift.0.35714286PD7238aPD7238b15995503691668842432GGACDH1CCDS10869.1r.684 685insac.493 494insAp.N166fs*2Insframeshift.0.41666667PD9579aPD9579b22726717361668842471GACDH1CCDS10869.1r.722+1a>ac.531+1G>Ap.?Subess splice0.22.PD13607aPD13607b21652909461668842663CCGTCDH1CCDS10869.1r.790_791insguc.599 600insGTp.P201fs*15Insframeshift.0.31034483PD14465aPD14465b22283643111668842714CAGCCDH1CCDS10869.1r.842 843delAGc.651 652delAGp.E218fs*4Delframeshift.0.38709677PD9597aPD9597b13227096671668844175CTCDH1CCDS10869.1r.954c>uc.763C>Tp.Q255*Subnonsense0.17.PD4985aPD4985b22589513981668844175CTCDH1CCDS10869.1r.954c>uc.763C>Tp.Q255*Subnonsense0.73.PD9063aPD9063b25447044441668844175CTCDH1CCDS10869.1r.954c>uc.763C>Tp.Q255*Subnonsense0.11.PD11740aPD11740b20225579201668844193GTCDH1CCDS10869.1r.972a>uc.781G>Tp.E261*Subnonsense0.24.PD11358aPD11358b25594889431668844245GCCDH1CCDS10869.1r.1023+1g>cc.832+1G>Cp.?Subess splice0.78.PD7214aPD7214b16420878501668845658TTACDH1CCDS10869.1r.1095_1096insac.904_905insAp.Y302fs*1Insframeshift.0.25490196PD18188aPD18188b21793138011668845723AGTCDH1CCDS10869.1r.1161_1169del GGAGUCAUCinsguc.970_978del GGAGTCATCinsGTp.G324fs*30Complexframeshift.0.22580645PD11342aPD11342b15512450991668846053ACACDH1CCDS10869.1r.1216delCc.1025delCp.L343fs*13Delframeshift.0.31818182PD4977aPD4977b22591691091668847276GACDH1CCDS10869.1r.1389a>ac.1198G>Ap.D400NSubmissense0.34.PD5936aPD5936b16003876741668847285GGCCDH1CCDS10869.1r.1398 1399inscc.1207_1208insCp.N405fs*14Insframeshift.0.77777778PD18756aPD18756b25373732651668849628CTCDH1CCDS10869.1r.1722c>uc.1531C>Tp.Q511*Subnonsense0.29.PD9589aPD9589b16011671811668856049TCTCDH1CCDS10869.1r.2049delCc.1858delCp. P620fs*11Delframeshift.0.42857143PD18049aPD18049b21066985761668856077GGACDH1CCDS10869.1r.2076_2077insac.1885 1886insAp.L630fs*33Insframeshift.0.28787879PD14442aPD14442b18440209501668857460CTCDH1CCDS10869.1r.2286c>uc.2095C>Tp.Q699*Subnonsense0.32.PD5960aPD5960b13063515431668857530GTCDH1CCDS10869.1r.2355+1g>uc.2164+1G>Tp.?Subess splice0.28.PD8618aPD8618b13706832731668862212GTCDH1CCDS10869.1r.2486+5g>uc.2295+5G>Tp.?Subess splice0.46.PD7209aPD7209b16381310331668867205GCDH1CCDS10869.1r.2644_2654del CUGAUACUGACc.2453_2463del CTGATACTGACp.D819fs*6Delframeshift.0.19354839PD11375aPD11375b17038835421668867284GTCGCDH1CCDS10869.1r.2723 2724delUCc.2532_2533delTCp.L845fs*15Delframeshift.0.40540541PD13416aPD13416b13153519201212871092CTCDKN1BCCDS8653.1r.696c>uc.319C>Tp.Q107*Subnonsense0.38.PD14472aPD14472b20565595111212871212CTCDKN1BCCDS8653.1r.816c>uc.439C>Tp.Q147*Subnonsense0.38.PD11341aPD11341b2414367523921971036CTCDKN2ACCDS6510.1r.593a>ac.322G>Ap.D108NSubmissense0.27.PD11336aPD11336b2415374729921971111GACDKN2ACCDS6510.1r.518c>uc.247C>Tp.H83YSubmissense0.14.PD18733aPD18733b2453038215921971120GACDKN2ACCDS6510.1r.509c>uc.238C>Tp.R80*Subnonsense0.6.PD13604aPD13604b22660399121942793085CGCICCCDS12601.1r.1017c>gc.977C>Gp.S326*Subnonsense0.21.PD5937aPD5937b12505079961954646887GACNOT3CCDS12880.1r.1661g>ac.58G>Ap.E20KSubmissense0.097.PD23565aPD23565b2368246951163807363TTGCREBBPCCDS10509.1r.4428 4429inscc.3623 3624insCp.Q1209fs*25Insframeshift.0.38095238PD5937aPD5937b1587361854163817720CTCCREBBPCCDS10509.1r.4055delAc.3250delAp.11084fs*15Delframeshift.0.24615385PD9694aPD9694b1210862299163820624GACREBBPCCDS10509.1r.3632c>uc.2827C>Tp.Q943*Subnonsense0.21.PD23579aPD23579b2416737661163823754GACREBBPCCDS10509.1r.3266c>uc.2461C>Tp.Q821*Subnonsense0.31.PD9009aPD9009b24068373161667645084CTCTCFCCDS10841.1r.793c>uc.349C>Tp.Q117*Subnonsense0.13.PD9541aPD9541b12858127601667645922CTCTCFCCDS10841.1r.1294c>uc.850C>Tp.H284YSubmissense0.61.PD9467aPD9467b18209724331667645924CGCTCFCCDS10841.1r.1296c>ac.852C>Gp.H284QSubmissense0.35.PD24223aPD24223b24728251951667650756CTCTCFCCDS10841.1r.1505c>uc.1061C>Tp.S354FSubmissense0.44.PD9570aPD9570b22611826751667670755GTCTCFCCDS10841.1r.2443+1g>uc.1999+1G>Tp.?Subess splice0.12.PD24326aPD24326b25369567177101833132GTCUX1CCDS5721.1r.1095g>uc.1057G>Tp.E353*Subnonsense0.5.PD4957aPD4957b22462029417101877410GACUX1CCDS5721.1r.3550g>ac.3512G>Ap.W1171*Subnonsense0.22.PD7207aPD7207b2248152330225458649GADNMT3ACCDS33157.1r.2862c>uc.2524C>Tp.Q842*Subnonsense0.31.PD18768aPD18768b2478680833225470903CACCTCGTCDNMT3ACCDS33157.1r.1189_1193+2del ACGAGauc.851_855+2del ACGAGgtp.?Deless splice.0.30434783PD5937aPD5937b12506082296139167714CGECT2LCCDS43508.1r.964c>ac.803C>Gp.S268*Subnonsense0.25.PD9568aPD9568b1853806315755233036CGEGFRCCDS5514.1r.1963c>ac.1786C>Gp.P596ASubmissense0.25.PD23564aPD23564b2418491806755241722GAEGFRCCDS5514.1r.2347a>ac.2170G>Ap.G724SSubmissense0.26.PD13425aPD13425b13198849161737868208CAERBB2CCDS32642.1r.1167c>ac.929C>Ap.S310YSubmissense0.15.PD11338aPD11338b12080741711737880220TCERBB2CCDS32642.1r.2502u>cc2264T>Cp.L755SSubmissense0.39.PD4072aPD4072b22560661911737880257CGERBB2CCDS32642.1r.2539c>gc.2301C>Gp.I767MSubmissense0.21.PD4072aPD4072b22560661921737880261GTERBB2CCDS32642.1r.2543a>uc.2305G>Tp. D769YSubmissense0.22.PD23565aPD23565b24173405381737880261GTERBB2CCDS32642.1r.2543a>uc.2305G>Tp.D769YSubmissense0.45.PD18049aPD18049b24065127721737881000GTERBB2CCDS32642.1r.2567a>uc.2329G>Tp.V777LSubmissense0.67.PD11386aPD11386b15680504631737881002GERBB2CCDS32642.1r.2569_2570ins aacuccccac.2331_2332ins GGCTCCCCAp.P780_Y781 insGSPInsinframe.0.19117647PD9575aPD9575b19207058851256478854GTERBB3CCDS31833.1r.503g>uc.310G>Tp.V104LSubmissense0.19.PD11348aPD11348b21750854421256478854GTERBB3CCDS31833.1r.503g>uc.310G>Tp.V104LSubmissense0.24.PD13306aPD13306b24648486181256478854GTERBB3CCDS31833.1r.503g>uc.310G>Tp.V104LSubmissense0.27.PD23564aPD23564b24183426161614026058CTERCC4CCDS32390.1r.1027c>uc.1018C>Tp.R340*Subnonsense0.23.PD18264aPD18264b24532319246152419923AGESR1CCDS5234.1r.1980a>gc.1610A>Gp.Y537CSubmissense0.23.PD13768aPD13768b24529576756152419926AGESR1CCDS5234.1r.1983a>gc.1613A>Gp.D538GSubmissense0.2.PD24320aPD24320b25752697446152419926AGESR1CCDS5234.1r.1983a>gc.1613A>Gp.D538GSubmissense0.34.PD24208aPD24208b23853064414153247289GAFBXW7CCDS3777.1r.1662c>uc.1513C>Tp.R505CSubmissense0.89.PD11379aPD11379b24154692394153268084GAFBXW7CCDS3777.1r.873c>uc.724C>Tp.Q242*Subnonsense0.44.PD9571aPD9571b18562782514153332811CAFBXW7CCDS3777.1r.294a>uc.145G>Tp.E49*Subnonsense0.76.PD11359aPD11359b131064275810123258034ATFGFR2CCDS7620.2r.2242u>ac.1650T>Ap.N550KSubmissense0.39.PD9597aPD9597b13226884241438061240GAFOXA1CCDS9665.1r.811c>uc.749C>Tp.S250FSubmissense0.22.PD13623aPD13623b15088382391438061240GAFOXA1CCDS9665.1r.811c>uc.749C>Tp.S250FSubmissense0.41.PD11386aPD11386b13232001221438061313CTFOXA1CCDS9665.1r.738a>ac.676G>Ap.D226NSubmissense0.31.PD9063aPD9063b25446830241438061313CTFOXA1CCDS9665.1r.738a>ac.676G>Ap.D226NSubmissense0.3.PD18247aPD18247b.1438061313CTFOXA1CCDS9665.1r.738a>ac.676G>Ap.D226NSubmissense0.094 33962.PD6016a2PD6016b.1438061313CTFOXA1CCDS9665.1r.738a>ac.676G>Ap.D226NSubmissense0.1111 1111.PD14433aPD14433b24939243191438061461GCFOXA1CCDS9665.1r.590c>gc.528C>Gp.1176MSubmissense0.25.PD5950aPD5950b1228278001371021785GAFOXP1CCDS2914.1r.2099c>uc.1573C>Tp.R525*Subnonsense0.15.PD9605aPD9605b1742397208371026113TCTFOXP1CCDS2914.1r.2034delGc.1508deIGp. R503fs*24Delframeshift.0.35135135PD13753aPD13753b2451864525371064695CTFOXP1CCDS2914.1r.1500+5g>ac.974+5G>Ap.?Subess splice0.14.PD11379aPD11379b2415456840371102914GTFOXP1CCDS2914.1r.819c>ac.293C>Ap.S98*Subnonsense0.49.PD13623aPD13623b1482874026108097752AGATA3CCDS31143.1r.703_721del19c.135_153del19p. E46fs*143Delframeshift.0.19444444PD5937aPD5937b1250416409108106058TAGATA3CCDS31143.1r.1449u>ac.881T>Ap.M294KSubmissense0.2.PD9063aPD9063b2544645668108106058TAGATA3CCDS31143.1r.1449u>ac.881T>Ap.M294KSubmissense0.18.PD13752aPD13752b1489656042108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.3PD4982aPD4982b1558585200108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.28571429PD4069aPD4069b1578712271108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.36170213PD7218aPD7218b1628359351108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.55555556PD9001aPD9001b1677955208108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.2972973PD7210aPD7210b1747391809108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.17391304PD9581aPD9581b1748195211108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.30985915PD13619aPD13619b1832199288108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.34146341PD4085aPD4085b2172392702108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.44PD23570aPD23570b2400736400108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.24324324PD18269aPD18269b2439664541108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.17021277PD7322aPD7322b2488385972108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.34PD9539aPD9539b2531735365108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.27777778PD13756aPD13756b2552598735108111432TCATGATA3CCDS31143.1r.1493-3_1493-2delcac.925-3_925-2delcap.?Deless splice.0.29545455PD6422aPD6422b1641080197108111484AGATA3CCDS31143.1r.1541_1542ins caaccacacuc.973_974ins CAACCACACTp.W329fs*27Insframeshift.0.125PD13625aPD13625b1813207266108111493CCTGATA3CCDS31143.1r.1550_1551insuc.982_983insTp.W329fs*24Insframeshift.0.37878788PD18734aPD18734b2410368888108111496TTGGATA3CCDS31143.1r.1553_1554insgc.985_986insGp.R330fs*23Insframeshift.0.32PD14456aPD14456b1483930818108111497GGATA3CCDS31143.1r.1554_1555ins aaaaac.986_987ins GAGGAp.N332fs*26Insframeshift.0.25PD11336aPD11336b1762439312108111499AGGAGATA3CCDS31143.1r.1557_1558delGGc.989_990delGGp.R330fs*22Delframeshift.0.23809524PD11388aPD11388b2553848069108111500GGAGATA3CCDS31143.1r.1557_1558insac.989_990insAp.R331fs*22Insframeshift.0.21052632PD11384aPD11384b1715682690108111513TTGGGATA3CCDS31143.1r.1570_1571 insggc.1002_1003insGGp.D336fs*21Insframeshift.0.21818182PD7209aPD7209b1637928061108111537TTGGATA3CCDS31143.1r.1594_1595insgc.1026_1027insGp.L344fs"9Insframeshift.0.23913043PD9761aPD9761b1311607618108111549CAGATA3CCDS31143.1r.1606c>ac.1038C>Ap.Y346*Subnonsense0.39.PD11389aPD11389b1675277083108111554TTTCGATA3CCDS31143.1r.1611_1612insucc.1043_1044insTCp.H349fs*8Insframeshift.0.3125PD14450aPD14450b2227138959108115704TAACATGATA3CCDS31143.1r.1622_1625del AACAc.1054_1057del AACAp.N352fs*3Delframeshift.0.27586207PD14458aPD14458b2461533029108115705AACAGATA3CCDS31143.1r.1623_1624delACc.1055_1056delACp.N352fs*19Delframeshift.0.32727273PD13310aPD13310b1561046913108115710ACAGATA3CCDS31143.1r.1628delCc.1060delCp. L355fs*1Delframeshift.0.52173913PD22362aPD22362b2314367145108115741AGATA3CCDS31143.1r.1659_1825del167c.1091_1257del167p.R365fs*87Delframeshift.0.19444444PD18264aPD18264b2434901164108115770CAACGATA3CCDS31143.1r.1688_1689delAAc.1120_1121delAAp.K375fs*6Delframeshift.0.14PD24214aPD24214b2479221831108115779CAGATA3CCDS31143.1r.1696c>ac.1128C>Ap.C376*Subnonsense0.35.PD11395aPD11395b1803239107108115814AGATA3CCDS31143.1r.1732_1754del23c.1164_1186del23p.K388fs*112Delframeshift.0.11904762PD7305aPD7305b2114075544108115850AGATA3CCDS31143.1r.1767_1768ins cauauccucccuaaac c.1199_1200insp.1407fs*106Insframeshift.0.22PD9847aPD9847b1686582986108115851CCAGATA3CCDS31143.1r.1768_1769insac.1200_1201insAp.M401fs*107Insframeshift.0.35897436PD11348aPD11348b2152289242108115853TTGGATA3CCDS31143.1r.1770_1771insgc.1202 1203insGp.S402fs*106Insframeshift.0.29787234PD11818aPD11818b1660202148108115873TTCGATA3CCDS31143.1r.1790_1791inscc.1222_1223insCp.P409fs*99Insframeshift.0.21052632PD11381aPD11381b1718253498108115874CCGGATA3CCDS31143.1r.1791_1792insgc.1223_1224insGp.P409fs*99Insframeshift.0.27083333PD6048aPD6048b2131239466108115874CCTGATA3CCDS31143.1r.1791_1792insuc.1223_1224insTp.P409fs*99Insframeshift.0.24561404PD11761aPD11761b2377830902108115874CCTGATA3CCDS31143.1r.1791_1792insuc.1223_1224insTp.P409fs*99Insframeshift.0.15625PD24320aPD24320b2560421339108115874CCAGATA3CCDS31143.1r.1791_1792insac.1223_1224insAp.P409fs*99Insframeshift.0.30434783PD9577aPD9577b1681948570108115892GGCGATA3CCDS31143.1r.1809_1810inscc.1241_1242insCp.H415fs*93Insframeshift.0.22058824PD9760aPD9760b1700278180108115911CCAGATA3CCDS31143.1r.1828_1829insac.1260_1261insAp.T421fs*87Insframeshift.0.28888889PD13764aPD13764b2515235648108115919TTGGATA3CCDS31143.1r.1836_1837insgc.1268_1269insGp.H424fs*84Insframeshift.0.22222222PD9000aPD9000b1727259349108115928CCAGATA3CCDS31143.1r.1845_1846insac.1277_1278insAp.S427fs*81Insframeshift.0.31578947PD4103aPD4103b.108115944TTGGATA3CCDS31143.1c.1295_1296insGp.P433fs*75InsFrameshift ins .PD9759aPD9759b1739163172108115952AACGATA3CCDS31143.1r.1869_1870inscc.1301_1302insCp.H435fs*73Insframeshift.0.15151515PD14467aPD14467b2039451005108115952AACCGATA3CCDS31143.1r.1869_1870insccc.1301_1302insCCp.H435fs*42Insframeshift.0.24444444PD7306aPD7306b2160956120108115955AACGATA3CCDS31143.1r.1872_1873inscc.1304_1305insCp.S437fs*71Insframeshift.0.19230769PD6711a2PD6711b2503502278108115955AACCGATA3CCDS31143.1r.1872_1873insccc.1304_1305insCCp.S437fs*40Insframeshift.0.41666667PD5964aPD5964b1580512876108115962CGATA3CCDS31143.1r.1879_1880ins aacauc.1311_1312ins AGCATp.M439fs*39Insframeshift.0.25641026PD6417aPD6417b1638709198108115982GTGGATA3CCDS31143.1r.1900delUc.1332delTp.*445fs*31Delframeshift.0.2962963PD9193aPD9193b2203330086108115982GGTGATA3CCDS31143.1r.1899_1900insuc.1331_1332insTp.*445fs*63Insframeshift.0.14PD9584aPD9584b240855368211533874TAHRASCCDS7698.1r.370a>uc.182A>Tp.Q61LSubmissense0.25.PD14472aPD14472b2043340041X44894228AAAGTAKDM6ACCDS14265.1r.659_660+2del AAauc.618_619+2del AAgtp.?Deless splice.0.2173913PD7321aPD7321b2244889631X44918338GAKDM6ACCDS14265.1r.1004a>ac.963G>Ap.W321*Subnonsense0.33.PD14458aPD14458b2462409174X44922769CCAKDM6ACCDS14265.1r.1671_1672insac.1630_1631insAp.L545fs*8Insframeshift.0.30769231PD9001aPD9001b2264385750X44929206CAKDM6ACCDS14265.1r.2347c>ac.2306C>Ap.S769*Subnonsense0.35.PD9568aPD9568b1853838523X44949176GCKDM6ACCDS14265.1r.3777+1g>cc.3736+1G>Cp.?Subess splice0.57.PD24333aPD24333b25759518521225398284CAKRASCCDS8703.1r.216a>uc.35G>Tp.G12VSubmissense0.3.PD7220aPD7220b22723259891711958295CTMAP2K4CCDS11162.1r.268c>uc.205C>Tp.Q69*Subnonsense0.43.PD11395aPD11395b18035077721711984670CAGAGCMAP2K4CCDS11162.1r.282-2_283del aaAGc.219-2_220del agAGp.?Deless splice.0.46428571PD4085aPD4085b21725751591711984670CAGCMAP2K4CCDS11162.1r.282-2_282-1del agc.219-2_219-1del aap.?Deless splice.0.45714286PD11369aPD11369b12106797001711984698GTMAP2K4CCDS11162.1r.307a>uc.244G>Tp.E82*Subnonsense0.78.PD11344aPD11344b21842293271712011144CTMAP2K4CCDS11162.1r.614c>uc.551C>Tp.S184LSubmissense0.31.PD9067aPD9067b25496876891712016583GTGMAP2K4CCDS11162.1r.783delUc.720delTp.S240fs*36Delframeshift.0.148936PD11339aPD11339b12118683211712032605GTMAP2K4CCDS11162.1r.1103+1g>uc.1040+1G>Tp.?Subess splice0.9.PD8982aPD8982b1517874520556111421TTCMAP3K1CCDS43318.1r.21_22inscc.21_22insCp.R8fs*16Insframeshift.0.19565217PD7202aPD7202b2135097917556111785GMAP3K1CCDS43318.1r.386_404del19c.386_404del19p.A130fs*49Delframeshift.0.17948718PD5956aPD5956b1606467257556155714TAATMAP3K1CCDS43318.1r.807_808delAAc.807_808delAAp.R270fs*30Delframeshift.0.47727273PD4605aPD4605b1655034490556155720GAAGMAP3K1CCDS43318.1r.813_814delAAc.813_814delAAp.R273fs*27Delframeshift.0.26315789PD18247aPD18247b2452585970556160616CACMAP3K1CCDS43318.1r.891delAc.891delAp.P298fs*14Delframeshift.0.14893617PD13427aPD13427b1677613489556160636AMAP3K1CCDS43318.1r.910_911ins caaaccacc.910_911ins CAAACCGCp.R307fs*8Insframeshift.0.2PD11740aPD11740b2022184858556160663CCAMAP3K1CCDS43318.1r.937_938insac.937_938insAp.R313fs*13Insframeshift.0.36585366PD6016a2PD6016b1634239916556160674GTACTGMAP3K1CCDS43318.1r.949_952del UACUc.949_952del TACTp.L318fs*4Delframeshift.0.18181818PD11394aPD11394b1611471410556160695GGTMAP3K1CCDS43318.1r.969_970insuc.969_970insTp.P324fs*2Insframeshift.0.32653061PD24302aPD24302b2484931733556160748TTGMAP3K1CCDS43318.1r.1022_1023insgc.1022_1023insGp.F341fs*44Insframeshift.0.15PD11394aPD11394b1611471411556161195GTATTGMAP3K1CCDS43318.1r.1065_1068del UAUUc.1065_1068del TATTp.H357fs*4Delframeshift.0.34090909PD3851aPD3851b2068615756556161230CTMAP3K1CCDS43318.1r.1099c>uc.1099C>Tp.Q367*Subnonsense0.51.PD5961aPD5961b1530637228556167803TTAMAP3K1CCDS43318.1r.1368_1369insac.1368_1369insAp.T457fs*4Insframeshift.0.19148936PD18776aPD18776b2517339991556167803TTAMAP3K1CCDS43318.1r.1368_1369insac.1368_1369insAp.T457fs*4Insframeshift.0.17647059PD7201aPD7201b1697092721556168471CMAP3K1CCDS43318.1r.1428_1437de IAGAAGAGUGUc.1428_1437del AGAAGAGTGTp.C479fs*5Delframeshift.0.2PD9570aPD9570b1598169622556170936CMAP3K1CCDS43318.1r.1764_1765ins cauaauauc.1764_1765ins CATGATGTp.S592fs*67Insframeshift.0.16666667PD9606aPD9606b1649876339556171035GTCTTCCCAGMAP3K1CCDS43318.1r.1864_1871del UCUUCCCAc.1864_1871del TCTTCCCAp.S622fs*21Delframeshift.0.32432432PD13419aPD13419b1690351759556171039TCTMAP3K1CCDS43318.1r.1868delCc.1868delCp.Q624fs*32Delframeshift.0.31428571PD13307aPD13307b1624857351556171066MAP3K1CCDS43318.1r.1895_1916del22 inscauaccc.1895_1916del22 insCATGCCp.V632fs*19Complexframeshift.0.18181818PD11756aPD11756b1507145260556171069GTMAP3K1CCDS43318.1r.1897a>uc.1897G>Tp.E633*Subnonsense0.21.PD4225aPD4225b2253030224556171091CAMAP3K1CCDS43318.1r.1919c>ac.1919C>Ap.S640*Subnonsense0.24.PD11359aPD11359b1709539727556171123TTAMAP3K1CCDS43318.1r.1951_1952insac.1951_1952insApY651fs*1Insframeshift.0.68965517PD13755aPD13755b1839326759556174927AAGMAP3K1CCDS43318.1r.2086_2087insgc.2086_2087insGp.S696fs*40Insframeshift.0.28571429PD13619aPD13619b1832870557556176975AACAMAP3K1CCDS43318.1r.2246 2247delACc.2246 2247delACp.N749fs*14Delframeshift.0.29268293PD9842aPD9842b1311919668556177017ATMAP3K1CCDS43318.1r.2287a>uc.2287A>Tp.R763*Subnonsense0.33.PD8828aPD8828b1672733083556177053CATCMAP3K1CCDS43318.1r.2324_2325delAUc.2324_2325delATp.I776fs*4Delframeshift.0.12820513PD13755aPD13755b1839326761556177563TCTMAP3K1CCDS43318.1r.2537deICc.2537delCp.T847fs*10Delframeshift.0.1372549PD5961aPD5961b1530637230556177654CTCMAP3K1CCDS43318.1r.2628delUc.2628delTp.L877fs*32Delframeshift.0.23404255PD13768aPD13768b2445129566556177685GGCATCTGTTCGMAP3K1CCDS43318.1r.2659_2668del GCAUCUGUUCc.2659_2668del GCATCTGTTCpA887fs*19Delframeshift.0.16981132PD6046aPD6046b1639971704556177762GAGMAP3K1CCDS43318.1r.2736delAc.2736delAp.G914fs*7Delframeshift.0.31343284PD9574aPD9574b1591041282556177784AATMAP3K1CCDS43318.1r.2757_2758insuc.2757 2758insTp.L920fs*10Insframeshift.0.34693878PD9606aPD9606b1649876343556178257CCAMAP3K1CCDS43318.1r.3230_3231insac.3230 3231insAp.N1079fs*2Insframeshift.0.30434783PD6418aPD6418b1761200038556178433CTCMAP3K1CCDS43318.1r.3407delUc.3407delTp.E1137fs*11Delframeshift.0.35714286PD18247aPD18247b2452585975556178474TATMAP3K1CCDS43318.1r.3448delAc.3448delAp.K1150fs*22Delframeshift.0.125PD4266aPD4266b1731822311556178528CMAP3K1CCDS43318.1r.3502_3514del AAAGAUGAUGUGAc.3502_3514del AAAGATGATGTGAp.K1168fs*18Delframeshift.0.1369863PD11756aPD11756b1491391835556178672TMAP3K1CCDS43318.1r.3646_3662del17c.3646_3662del17p.I1216fs*17Delframeshift.0.15384615PD13623aPD13623b1483544710556179438CCTMAP3K1CCDS43318.1r.3751_3752insuc.3751_3752insTp.G1252fs*21Insframeshift.0.26785714PD11343aPD11343b2556047957556179500TTAMAP3K1CCDS43318.1r.3813_3814insac.3813_3814insAp.Q1273fs*11Insframeshift.0.22222222PD13768aPD13768b2445129568556180550AGAGATAMAP3K1CCDS43318.1r.3880_3884del GAGAUc.3880_3884del GAGATp.E1294fs*13Delframeshift.0.18PD18776aPD18776b2525053934556180614GTMAP3K1CCDS43318.1r.3943a>uc.3943G>TpE1315"Subnonsense0.23.PD9574aPD9574b1591041285556181844CMAP3K1CCDS43318.1r.4068_4069ins cuuucauaucuc.4068_4069ins CTTTCGTATCTp.H1361fs*20Insframeshift.0.25PD17994aPD17994b1823240809556183234CTMAP3K1CCDS43318.1r.4144c>uc.4144C>Tp.Q1382*Subnonsense0.19.PD13619aPD13619b1832870560556183241TATMAP3K1CCDS43318.1r.4152delAc.4152delAp.R1385fs*37Delframeshift.0.29230769PD13427aPD13427b1677613496556183330GCGMAP3K1CCDS43318.1r.4241delCc.4241delCp.A1414fs*8Delframeshift.0.17391304PD13618aPD13618b1829787035556183346AAGMAP3K1CCDS43318.1r.4256_4257insgc.4256_4257insGp.V1420fs*12Insframeshift.0.19354839PD13618aPD13618b1829787040556189415GGAMAP3K1CCDS43318.1r.4447_4448insac.4447_4448insAp.D1483fs*40Insframeshift.0.34615385PD4977aPD4977b1937107384556189434TMAP3K1CCDS43318.1r.4467_4497del31c.4467_4497del31p.L1491fs*3Delframeshift.0.15789474PD24307aPD24307b24857949606131908954AGAMED23CCDS5147.1r.4151deICc.3971delCp.A1324fs*2Delframeshift.0.31372549PD18116aPD18116b25252380896131917741GAMED23CCDS5147.1r.2875c>uc.2695C>Tp.R899*Subnonsense0.41.PD7238aPD7238b15999490286131919439TATMED23CCDS5147.1r.2774delUc.2594delTp.L865fs*1Delframeshift.0.5PD23564aPD23564b23378267106131919845ATAMED23CCDS5147.1r.2456delAc.2276delAp.N759fs*12Delframeshift.0.22222222PD24216aPD24216b24842228146131923421CCTTMED23CCDS5147.1r.2211_2212insaac.2031_2032insAAp.A678fs*7Insframeshift.0.52941176PD11762aPD11762b13339212566131927766TCMED23CCDS5147.1r.1402-2a>ac.1222-2A>Gp.?Subess splice0.3.PD9578aPD9578b25370984236131931387CAMED23CCDS5147.1r.1057-1a>uc.877-1G>Tp.?Subess splice0.24.PD7322aPD7322b24884455501164573730CCAGGCCTGCMEN1CCDS8083.1r.1534_1541del CAGGCCUGc.1030_1037de1 CAGGCCTGp.Q344fs*25Delframeshift.0.47619176PD24193aPD24193b2398176351337090394GCMLH1CCDS2663.1r.2206-1a>cc.1990-1G>Cp.?Subess splice0.3.PD6412aPD6412b1777477609337090896AMLH1CCDS2663.1r.2319+389_2409 del1170c.2103+389_2193 del1170p.?Deless splice.0.14285714PD4109aPD4109b18222625601249415846GAMLL2CCDS44873.1r.16501c>uc.16501C>Tp.R5501*Subnonsense0.44.PD6412aPD6412b17770562541249422631CTGCMLL2CCDS44873.1r.14360_14361del CAc.14360_14361del CAp.T4787fs*29Delframeshift.0.27272727PD4006aPD4006b21196183771249422656TCCTTTGCTMLL2CCDS44873.1r.14330_14336del GCAAAGGc.14330_14336del GCAAAGGp.G4777fs*18Delframeshift.0.31818182PD6412aPD6412b17770562561249426221CAGCMLL2CCDS44873.1r.12265_12266del CUc.12265_12266del CTp.L4089fs*17Delframeshift.0.24637681PD13754aPD13754b24476614741249436523CAMLL2CCDS44873.1r.5782+1g>uc.5782+1G>Tp.?Subess splice0.19.PD11389aPD11389b16759904837151845466AMLL3CCDS5931.1r.13746_13764del 19c.13527_13545del 19p.4509fs*2Delframeshift.0.28813559PD13771aPD13771b18376120367151845485CMLL3CCDS5931.1r.13717_13745del 29c.13498_13526de1 29p.T4500fs*4Delframeshift.0.25806452PD18733aPD18733b24462559197151845958ATAMLL3CCDS5931.1r.13272delAc.13053delAp.K4351fs*5Delframeshift.0.21428571PD7249aPD7249b12540279977151846177GAMLL3CCDS5931.1r.13054c>uc.12835C>Tp.Q4279*Subnonsense0.64.PD7217aPD7217b22588890617151856024GCMLL3CCDS5931.1r.11813c>ac.11594C>Gp.S3865*Subnonsense0.19.PD7210aPD7210b22609724877151860212GAMLL3CCDS5931.1r.10669c>uc.10450C>Tp.Q3484*Subnonsense0.5.PD5937aPD5937b12506258587151860728GAMLL3CCDS5931.1r.10153c>uc.9934C>Tp.Q3312*Subnonsense0.33.PD24333aPD24333b25483997347151860863TTCMLL3CCDS5931.1r.10017_10018insgc.9798_9799insGp.13267fs*59Insframeshift.0.51351351PD13753aPD13753b24414739087151864252CMLL3CCDS5931.1r.9932_9947del16c.9713_9728del16p.T3238fs*6Delframeshift.0.10344828PD13758aPD13758b24336702507151873725GMLL3CCDS5931.1r.9016_9031 del16c.8797_8812del16p.R2933fs*21Delframeshift.0.23 809524PD13425aPD13425b13199952147151873749GCMLL3CCDS5931.1r.9008c>ac.8789C>Gp.S2930*Subnonsense0.15.PD18756aPD18756b25374297437151873888GAMLL3CCDS5931.1r.8869c>uc.8650C>TpR2884"Subnonsense0.18.PD6414aPD6414b17531777267151874147CTCMLL3CCDS5931.1r.8609delAc.8390delAp.K2797fs*26Delframeshift.0.24193548PD6412aPD6412b17777981987151874147CTCMLL3CCDS5931.1r.8609delAc.8390delAp.K2797fs*26Delframeshift.0.16326531PD23564aPD23564b23379134667151874147CTCMLL3CCDS5931.1r.8609delAc.8390delAp.K2797fs*26Delframeshift.0.31147541PD13762aPD13762b14948482067151875059CGCMLL3CCDS5931.1r.7697delCc.7478delCp.P2493fs*22Delframeshift.0.26190476PD4103aPD4103b20570443087151876918CTMLL3CCDS5931.1r.7661+1g>ac.7442+1G>Ap.?Subess splice0.2.PD11344aPD11344b21843287847151878287GAMLL3CCDS5931.1r.6877c>uc.6658C>Tp.Q2220*Subnonsense0.35.PD24204aPD24204b23857841607151878863GAMLL3CCDS5931.1r.6301c>uc.6082C>Tp.R2028*Subnonsense0.41.PD9541aPD9541b17172601767151879253AMLL3CCDS5931.1r.5901_5910del AAUGGAUCCAc.5682_5691 del AATGGATCCAp.D1896fs*40Delframeshift.0.14583333PD13304aPD13304b15675865547151879521ACTAMLL3CCDS5931.1r.5641_5642del AGc.5422_5423del AGp.P1809fs*8Delframeshift.0.25PD11372aPD11372b12132572447151884502GCMLL3CCDS5931.1r.5072c>ac.4853C>GpS1618*Subnonsense0.5.PD24204aPD24204b23831233237151891329AATMLL3CCDS5931.1r.4743_4744insac.4524_4525insAp.L1509fs*3Insframeshift.0.35PD10011aPD10011b25093945587151932901CAMLL3CCDS5931.1r.2988+1g>uc.2769+1G>Tp.?Subess splice0.25.PD11402aPD11402b16938132987151932992CTCMLL3CCDS5931.1r.2897delAc.2678delAp.K893fs*20Delframeshift.0.1971831PD4981aPD4981b22487214427151945226CAMLL3CCDS5931.1r.2512a>uc.2293G>Tp.E765*Subnonsense0.2.PD11352aPD11352b16928839997151945631TMLL3CCDS5931.1r.2082_2106del 25c.1863_1887del 25p. N621 fs*6Delframeshift.0.4PD22364aPD22364b23165159287151946974ACTATAMLL3CCDS5931.1r.2015_2018del AUAGc.1796_1799del ATAGp.D599fs*12Delframeshift.0.66PD11336aPD11336b24153670737151949719GAMLL3CCDS5931.1r.1600c>uc.1381C>Tp.Q461*Subnonsense0.19.PD9589aPD9589b16015772557151949738CCAMLL3CCDS5931.1r.1580_1581insuc.1361_1362insTp.I455fs*3Insframeshift.0.16PD23561aPD23561b24034706407151949758GAMLL3CCDS5931.1r.1561c>uc.1342C>Tp.Q448*Subnonsense0.27.PD18046aPD18046b21193923917151960177GGTMLL3CCDS5931.1r.1441_1442insac.1222_1223insAp.T408fs*3Insframeshift.0.36363636PD9064aPD9064b23045075237151960206TCTMLL3CCDS5931.1r.1412delGc.1193delGp.G398fs*7Delframeshift.0.77380952PD13298aPD13298b15525588937152007138ACAMLL3CCDS5931.1r.980delGc.761delGp.R254fs*7Delframeshift.0.1627907PD5944aPD5944b15533633747152008968ATAMLL3CCDS5931.1r.872delAc.653delAp.D218fs*43Delframeshift.0.35897436PD6412aPD6412b17777983747152012385CTCMLL3CCDS5931.1r.646delAc.427delAp.S143fs*3Delframeshift.0.13333333PD4967aPD4967b16057590606168281125CTCMLLT4CCDS47516.1r.823delUc.823delTp.F275fs*7Delframeshift.0.10344828PD4005aPD4005b20688395976168297599CTMLLT4CCDS47516.1r.1261c>uc.1261C>Tp.Q421*Subnonsense0.12.PD9575aPD9575b18544970426168303032ATATTCAMLLT4CCDS47516.1r.1614_1618del UAUUCc.1614_1618del TATTCp.D538fs*2Delframeshift.0.21276596PD22251aPD22251b23094550756168307939AMLLT4CCDS47516.1r.1737_1750del GCAGCCAGAUUAUCc1737 _1750del GCAGCCAGATTATCp.P581fs*12Delframeshift.0.53333333PD14457aPD14457b18347597076168315877AATMLLT4CCDS47516.1r.2305_2306insuc.2305_2306insTp.M769fs*32Insframeshift.0.46153846PD13771aPD13771b18405291246168315898ATMLLT4CCDS47516.1r.2326a>uc.2326A>Tp.R776*Subnonsense0.57.PD24189aPD24189b24899810996168325728TATMLLT4CCDS47516.1r.3033delAc.3033delAp.K1013fs*20Delframeshift.0.23255814PD6043aPD6043b17389276896168347439GCMLLT4CCDS47516.1r.3388_3399del CUCUAUAAUAAUinscc.3388_3399del CTCTATAATAATinsCp.Y1131fs*7Complexframeshift.0.62903226PD5937aPD5937b1250512507247643501CTMSH2CCDS1834.1r.1232c>uc.1009C>Tp.Q337*Subnonsense0.2.PD5937aPD5937b1250512511247690201CAMSH2CCDS1834.1r.1641c>ac.1418C>Ap.S473*Subnonsense0.33.PD22251aPD22251b23098652761715961268GANCOR1CCDS11175.1r.6379c>uc.6121C>Tp.Q2041*Subnonsense0.34.PD11740aPD11740b20225596661715974791GANCOR1CCDS11175.1r.4342c>uc.4084C>Tp.Q1362*Subnonsense0.38.PD4072aPD4072b22560656001715983280GANCOR1CCDS11175.1r.3757c>uc.3499C>Tp.Q1167*Subnonsense0.25.PD5961aPD5961b22514481101715983936CANCOR1CCDS11175.1r.3541a>uc.3283G>Tp E1095*Subnonsense0.21.PD24217aPD24217b25031877901716004595CANCOR1CCDS11175.1r.2917a>uc.2659G>Tp.E887*Subnonsense0.18.PD11745aPD11745b24550194411716022772CGCNCOR1CCDS11175.1r.2137delCc.1879delCp.R627fs*14Delframeshift.0.20833333PD3945aPD3945b21532194791716024380GNCOR1CCDS11175.1r.2049_2095del47c.1791_1837del47p.A599fs*23Delframeshift.0.41666667PD18047aPD18047b21286057901716029427CANCOR1CCDS11175.1r.1861a>uc.1603G>Tp.E535*Subnonsense0.45.PD13625aPD13625b18134966971716029445CCTNCOR1CCDS11175.1r.1842_1843insac.1584_1585insAp.E529fs*7Insframeshift.0.46PD24320aPD24320b25606065481716029445CTCNCOR1CCDS11175.1r.1842delAc.1584delAp.E529fs*26Delframeshift.0.4516129PD24215aPD24215b24954870001716029452TTCTNCOR1CCDS11175.1r.1834_1835delGAc.1576_1577delGAp.E526fs*9Delframeshift.0.4375PD4605aPD4605b16547579511716029456GGTNCOR1CCDS11175.1r.1831_1832insac.1573_1574insAp.T525fs*11Insframeshift.0.38235294PD23564aPD23564b23372992491729486049GAGNF1CCDS42292.1r.610delAc.227delAp.N78fs*7Delframeshift.0.48387097PD13163aPD13163b21844155641729527439GCNF1CCDS42292.1r.1272-1a>cc.889-1G>Cp.?Subess splice0.56.PD24202aPD24202b23973945261729550505CTNF1CCDS42292.1r.2148c>uc.1765C>Tp.Q589*Subnonsense0.15.PD4976aPD4976b22544856871729557277GTNF1CCDS42292.1r.3374-1a>uc.2991-1G>Tp.?Subess splice0.86.PD7426aPD7426b18527653221729576134CANF1CCDS42292.1r.4490c>ac.4107C>ApY1369*Subnonsense0.67.PD22036aPD22036b24170674981729586092GTNF1CCDS42292.1r.4758a>uc.4375G>Tp.E1459*Subnonsense0.24.PD6719aPD6719b17724764691729652922AATTGTANF1CCDS42292.1r.5304_5308del AUUGUc.4921_4925del ATTGTp.I641fs*9Delframeshift.0.33333333PD4605aPD4605b16547609641729661916GGTNF1CCDS42292.1r.6256_6257insuc.5873_5874insTp.C1960fs*4Insframeshift.0.32258065PD7240aPD7240b25090815721729677227CTNF1CCDS42292.1r.7731c>uc.7348C>Tp.R2450*Subnonsense0.4.PD5934aPD5934b22533796162230035202GTNF2CCDS13861.1r.804+1g>uc.363+1G>Tp.?Subess splice0.21.PD9568aPD9568b18535987839139390935AGANOTCH1CCDS43905.1r.7331delCc.7255delCp.G2420fs*2Delframeshift.0.71428571PD4315aPD4315b17301740609139397631TTANOTCH1CCDS43905.1r.5243+2_43+ 3insuc.5167+2_5167+ 3insTp.?Insess splice.0.46875PD23564aPD23564b23369222841120458084ACTANOTCH2CCDS908.1r.7479_7480del AGc.7259_7260del AGp.E2420fs*3Delframeshift.0.34782609PD5950aPD5950b12280917331120458396GANOTCH2CCDS908.1r.7169c>uc.6949C>Tp.Q2317*Subnonsense0.2.PD8619aPD8619b15356021931120458477CANOTCH2CCDS908.1r.7088a>uc.6868G>Tp.E2290*Subnonsense0.61.PD13298aPD13298b12163880631120458549CANOTCH2CCDS908.1r.7016a>uc.6796G>Tp.E2266*Subnonsense0.9.PD8618aPD8618b13706487431120466609TGNOTCH2CCDS908.1r.4732-2a>cc.4512-2A>Cp.?Subess splice0.22.PD11345aPD11345b21846779841120547967GANOTCH2CCDS908.1r.620c>uc.400C>Tp.Q134*Subnonsense0.32.PD24212aPD24212b24704872111115258748CANRASCCDS877.1r.288a>uc.34G>Tp.G12CSubmissense0.21.PD11340aPD11340b16613634571623625322TACCTPALB2CCDS32406.1r.3401_3401+2del Gauc.3201_3201+2del Ggtp.?Deless splice.0.10769231PD24205aPD24205b23979007271623641218GAPALB2CCDS32406.1r.2457c>uc.2257C>Tp.R753*Subnonsense0.38.PD24212aPD24212b24685412991623646654GAAGPALB2CCDS32406.1r.1411_1412delUUc.1211_1212delTTp.F404fs*7Delframeshift.0.32608696PD8980aPD8980b1721439714352685791AGAPBRM1CCDS2859.1r.683delCc.680delCp.P227fs*2Delframeshift.0.275PD9591aPD9591b2377601952X133512118TATPHF6CCDS14639.1r.425delAc.223delAp.R76fs*5Delframeshift.0.17948718PD5930aPD5930b2262004442X133559304GTPHF6CCDS14639.1r.1244a>uc.1042G>Tp.G348*Subnonsense0.11.PD4970aPD4970b15973141823178916919TGAACCATPIK3CACCDS43171.1r.464_469del GAACCAc307_312del GAACCAp.E103_P104 delEPDelinframe.0.18181818PD11342aPD11342b15514839823178916923CCAGTAGCPIK3CACCDS43171.1r.468_473del CAGUAGc.311_316del CAGTAGp.P104_G106 delinsRDelcomplex sub.0.425PD13619aPD13619b18402823493178916924CTPIK3CACCDS43171.1r.468c>uc.311C>Tp.P104LSubmissense0.45.PD4967aPD4967b22464477693178916924CTPIK3CACCDS43171.1r.468c>uc311C>Tp.P104LSubmissense0.18.PD24320aPD24320b25752556393178916924CTPIK3CACCDS43171.1r.468c>uc.311C>Tp.P104LSubmissense0.43.PD4605aPD4605b16549630263178916928AGGCAACCGTAPIK3CACCDS43171.1r.473_481del GGCAACCGUc.316_324del GGCAACCGTp.G106_R108 delGNRDelinframe.0.3442623PD13758aPD13758b24417934313178916929GCPIK3CACCDS43171.1r.473a>cc.316G>Cp.G106RSubmissense0.19.PD17994aPD17994b18074695303178916943AAAGATCAPIK3CACCDS43171.1r.488_493del AAGAUCc.331_336del AAGATCp.K111_I112 delKIDelinframe.0.1 6666667PD9595aPD9595b16224261923178916945AGATCCTAPIK3CACCDS43171.1r.490_495del GAUCCUc.333_338del GATCCTp.K111_L113 delinsNDelcomplex sub.0.12307692PD4844aPD4844b318336209423178916949CCTCAATCPIK3CACCDS43171.1r.494_499del CUCAAUc.337_342del CTCAATp.L113_N114 delLNDelinframe.0.23728814PD6720aPD6720b22501919943178917478GAPIK3CACCDS43171.1r.510a>ac.353G>Ap.G118DSubmissense0.21.PD24329aPD24329b25761374633178921548GAPIK3CACCDS43171.1r.1187a>ac.1030G>Ap.V344MSubmissense0.17.PD11380aPD11380b12228240013178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap.N345KSubmissense0.35.PD11816aPD11816b13157841823178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap. N345KSubmissense0.36.PD13631aPD13631b15078231733178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap. N345KSubmissense0.4.PD11366aPD11366b15082076303178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap. N345KSubmissense0.47.PD14473aPD14473b20559874083178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap.N345KSubmissense0.3.PD18050aPD18050b21875893613178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap. N345KSubmissense0.44.\PD7219aPD7219b22489094003178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap. N345KSubmissense0.13.PD4261aPD4261b22562052293178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap.N345KSubmissense0.28.PD4969aPD4969b.3178921553TAPIK3CACCDS43171.1r.1192u>ac.1035T>Ap. N345KSubmissense0.15.PD18247aPD18247b24568878473178922324GAPIK3CACCDS43171.1r.1250a>ac.1093G>Ap.E365KSubmissense0.15.PD18047aPD18047b21286535733178922328CGPIK3CACCDS43171.1r.1254c>ac.1097C>Gp.P366RSubmissense0.25.PD11372aPD11372b12132346563178927980TCPIK3CACCDS43171.1r.1415u>cc.1258T>Cp.C420RSubmissense0.43.PD13425aPD13425b13199407053178927980TCPIK3CACCDS43171.1r.1415u>cc.1258T>Cp.C420RSubmissense0.76.PD11465aPD11465b21865128173178927980TCPIK3CACCDS43171.1r.1415u>cc.1258T>Cp.C420RSubmissense0.32.PD22361aPD22361b24211512473178927980TCPIK3CACCDS43171.1r.1415u>cc.1258T>Cp.C420RSubmissense0.23.PD11767aPD11767b.3178927980TCPIK3CACCDS43171.1r.1415u>cc.1258T>Cp.C420RSubmissense0.09.PD9844aPD9844b.3178927980TCPIK3CACCDS43171.1r.1415u>cc.1258T>Cp.C420RSubmissense0.44.PD13753aPD13753b24412283143178928070CPIK3CACCDS43171.1 r.1506_1520del c.1349_1363delp.H450_D454 delHGLEDDelinframe.0.18PD13626aPD13626b14934773663178928073GPIK3CACCDS43171.1 r.1509_1523del c.1352_1366delp.G451_L456 delinsVDelcomplex sub.0.28571429PD4977aPD4977b22592148113178928079GAPIK3CACCDS43171.1r.1514a>ac.1357G>Ap.E453KSubmissense0.41.PD24193aPD24193b23981822083178928079GAPIK3CACCDS43171.1r.1514g>ac.1357G>Ap.E453KSubmissense0.12.PD9063aPD9063b25447781573178928079GAPIK3CACCDS43171.1r.1514g>ac.1357G>Ap.E453KSubmissense0.19.PD23558aPD23558b23424002953178928080ATPIK3CACCDS43171.1r.1515a>uc.1358A>Tp.E453VSubmissense0.12.PD13299aPD13299b12128965983178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.38.PD11352aPD11352b12392667643178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.55.PD11359aPD11359b13106936813178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.42.PD13623aPD13623b15088887903178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.28.PD13760aPD13760b15091790393178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.27.PD18100aPD18100b18407089883178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.23.PD4267aPD4267b22466250343178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.32.PD5951aPD5951b22597645093178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.56.PD9579aPD9579b22727288993178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.16.PD6416aPD6416b22730169673178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap. E542KSubmissense0.11PD13629aPD13629b23765775243178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.42.PD23561aPD23561b24034163683178936082GAPIK3CACCDS43171.1r.1781a>ac.1624G>Ap.E542KSubmissense0.35.PD9755aPD9755b24077681223178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.38.PD17981aPD17981b24270591093178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.67.PD11745aPD11745b24601674693178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.38.PD9002aPD9002b24642532763178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.44.PD24225aPD24225b24980677003178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.19.PD3905aPD3905b25445617473178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.15.PD9067aPD9067b25515253193178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.14.PD11343aPD11343b25590905433178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.41.PD24333aPD24333b25760075613178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.38.PD13757aPD13757b3178936082GAPIK3CACCDS43171.1r.1781g>ac.1624G>Ap.E542KSubmissense0.11.PD5937aPD5937b12505647203178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.2.PD9606aPD9606b13156171823178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.48.PD11402aPD11402b13163564493178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.39.PD13762aPD13762b15085175843178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.26.PD9467aPD9467b18210128093178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.23.PD11395aPD11395b18215301823178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.37.PD13770aPD13770b18218053843178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.54.PD18748aPD18748b18236435293178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.27.PD14472aPD14472b20565899253178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.3.PD13162aPD13162b21211981823178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.39.PD18046aPD18046b21380734863178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.77.PD7209aPD7209b22493283313178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.4.PD6417aPD6417b22508824043178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.68.PD4225aPD4225b22530176193178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.21.PD4315aPD4315b22531863183178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.29.PD4976aPD4976b22545446523178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.61.PD4965aPD4965b22555330653178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.3.PD3989aPD3989b22558685873178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.39.PD4072aPD4072b22560898163178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.13.PD4982aPD4982b22624627003178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.59.PD11379aPD11379b24154621793178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.44.PD18749aPD18749b24338713863178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.38.PD4978aPD4978b24395402773178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.44.PD13767aPD13767b24558214163178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.39.PD24307aPD24307b24880554853178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.2.PD11327aPD11327b25113859233178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.31.PD18116aPD18116b25252084143178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.4.PD9578aPD9578b25370755683178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.21.PD24327aPD24327b25757634663178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.44.PD24329aPD24329b25761374653178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.63.PD9541aPD9541b.3178936091GAPIK3CACCDS43171.1r.1790a>ac.1633G>Ap.E545KSubmissense0.1.PD13165aPD13165b21459932023178936092ACPIK3CACCDS43171.1r.1791a>cc.1634A>Cp.E545ASubmissense0.41.PD4986aPD4986b22577752573178936092ACPIK3CACCDS43171.1r.1791a>cc.1634A>Cp.E545ASubmissense0.41.PD9574aPD9574b22608523903178936092ACPIK3CACCDS43171.1r.1791a>cc.1634A>Cp.E545ASubmissense0.24.PD24207aPD24207b23984432363178936092ACPIK3CACCDS43171.1r.1791a>cc.1634A>Cp.E545ASubmissense0.44.PD11345aPD11345b21847837783178936093GCPIK3CACCDS43171.1r.1792a>cc.1635G>Cp.E545DSubmissense0.35.PD24199aPD24199b23896127303178936093GCPIK3CACCDS43171.1r.1792a>cc.1635G>Cp.E545DSubmissense0.3.PD11345aPD11345b21847837793178936094CAPIK3CACCDS43171.1r.1793c>ac.1636C>Ap.Q546KSubmissense0.35.PD4069aPD4069b22512021503178936094CAPIK3CACCDS43171.1r.1793c>ac.1636C>Ap.Q546KSubmissense0.41.PD11381aPD11381b12113412143178936095ACPIK3CACCDS43171.1r.1794a>cc.1637A>Cp.Q546PSubmissense0.3.PD13618aPD13618b18379127483178937422TCPIK3CACCDS43171.1r.1967u>cc.1810T>Cp.C604RSubmissense0.11.PD5937aPD5937b12505647213178938934GAPIK3CACCDS43171.1r.2333a>ac.2176G>Ap.E726KSubmissense0.38.PD24333aPD24333b25760075623178938934GAPIK3CACCDS43171.1r.2333a>ac.2176G>Ap.E726KSubmissense0.21.PD9063aPD9063b.3178938934GAPIK3CACCDS43171.1r.2333a>ac.2176G>Ap.E726KSubmissense0.07.PD24189aPD24189b24903717193178941923CAPIK3CACCDS43171.1r.2399c>ac.2242C>Ap.L748ISubmissense0.33.PD18776aPD18776b25250429953178951957GAPIK3CACCDS43171.1r.3169a>ac.3012G>Ap.M1004ISubmissense0.2.PD4844aPD4844b318397703783178952064TCPIK3CACCDS43171.1r.3276u>cc.3119T>Cp.M1040TSubmissense0.42.PD4607aPD4607b22495023703178952074GAPIK3CACCDS43171.1r.3286g>ac.3129G>Ap.M1043ISubmissense0.091.PD13770aPD13770b18218053853178952084CTPIK3CACCDS43171.1r.3296c>uc.3139C>Tp.H1047YSubmissense0.17.PD24193aPD24193b23981822093178952084CTPIK3CACCDS43171.1r.3296c>uc.3139C>Tp.H1047YSubmissense0.14.PD11338aPD11338b12081134143178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.23.PD9756aPD9756b12103203743178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.36.PD9544aPD9544b12170560133178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.28.PD8828aPD8828b12285401683178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.18.PD13426aPD13426b13068699363178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.27.PD6016a2PD6016b13191353713178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.33.PD11386aPD11386b13232408203178952085ATPIK3CACCDS43171.1r.3297a>uc.3140A>Tp.H1047LSubmissense0.24.PD11762aPD11762b13338896453178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.4.PD8623aPD8623b13834944813178952085ATPIK3CACCDS43171.1r.3297a>uc.3140A>Tp.H1047LSubmissense0.27.PD8622aPD8622b13929931793178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.28.PD8617aPD8617b15349979133178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.19.PD18751aPD18751b18219016793178952085ATPIK3CACCDS43171.1r.3297a>uc.3140A>Tp.H1047LSubmissense0.24.PD13618aPD13618b18379127493178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.44.PD11364aPD11364b18384547423178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.42.PD13619aPD13619b18402823523178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.43.PD4076aPD4076b18508411773178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.29.PD17991aPD17991b18604159773178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.31.PD4085aPD4085b20683810933178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.62.PD11347aPD11347b21859457213178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.26.PD4967aPD4967b22464477743178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.14.PD7199aPD7199b22468087853178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.37.PD5928aPD5928b22480431453178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.37.PD4985aPD4985b22589788723178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.61.PD4977aPD4977b22592148133178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.36.PD9570aPD9570b22612464953178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.16.PD7201aPD7201b22613746373178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.41.PD4266aPD4266b22629475133178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.28.PD13602aPD13602b22679028633178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.51.PD14465aPD14465b22691038223178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.2.PD24204aPD24204b23857490573178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.59.PD24199aPD24199b23896127323178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.49.PD9009aPD9009b24069992663178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.18.PD8965aPD8965b24100592753178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.26.PD18734aPD18734b24118785113178952085ATPIK3CACCDS43171.1r.3297a>uc.3140A>Tp.H1047LSubmissense0.15.PD6041aPD6041b24145409703178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.21.PD23579aPD23579b24167998103178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.22.PD22359aPD22359b24175011793178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.14.PD18269aPD18269b24474283593178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.3.PD13768aPD13768b24529330323178952085ATPIK3CACCDS43171.1r.3297a>uc.3140A>Tp.H1047LSubmissense0.26.PD18258aPD18258b24559107513178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.38.PD18247aPD18247b24568878513178952085ATPIK3CACCDS43171.1r.3297a>uc.3140A>Tp.H1047LSubmissense0.18.PD11744aPD11744b24624964343178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.36.PD13304aPD13304b24653942603178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.32.PD18768aPD18768b24793619323178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.51.PD14459aPD14459b24875919553178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.4.PD24189aPD24189b24903717213178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.38.PD24215aPD24215b24962595473178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.29.PD24217aPD24217b25032480583178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.32.PD24224aPD24224b25033957513178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.54.PD6466bPD6466a25080510013178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.15.PD18754aPD18754b25233540743178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.53.PD24326aPD24326b25369276663178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.29.PD11766aPD11766b25372613973178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.12.PD18756aPD18756b25374057033178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.23.PD4192aPD4192b25592233723178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.31.PD24336aPD24336b25751262323178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.12.PD24302aPD24302b25756088883178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.43.PD24194aPD24194b. .3178952085AGPIK3CACCDS43171.1r.3297a>ac.3140A>Gp.H1047RSubmissense0.0612 2449.PD18022aPD18022b. .3178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.0625.PD9584aPD9584b. .3178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.16.PD9591aPD9591b. .3178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.16.PD8615aPD8615b. .3178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.16.PD14441aPD14441b. .3178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.29.PD14439aPD14439b.3178952085AGPIK3CACCDS43171.1r.3297a>gc.3140A>Gp.H1047RSubmissense0.35.PD18728aPD18728b24638033873178952086TAPIK3CACCDS43171.1r.3298u>ac.3141T>Ap.H1047QSubmissense0.22.PD4847aPD4847b21945706781567522699AAGPIK3R1CCDS3993.1r.238_239insgc.196_197insGp.D68fs*38Insframeshift.0.16438356PD6412aPD6412b1777631276567522740GAGPIK3R1CCDS3993.1r.280delAc.238delAp.I82fs*32Delframeshift.0.33333333PD5925aPD5925b1646623863567588154ACAPIK3R1CCDS3993.1r.1027delCc.985delCp.Q329fs*15Delframeshift.0.31428571PD7217aPD7217b1941822104567589494TPIK3R1CCDS3993.1r.1342-42_1467 +52del220c.1300-42_1425+52 del220p.?Deless splice.0.15789474PD6042aPD6042b1702505346567589568CPIK3R1CCDS3993.1r.1374_1391 del 18c.1332_1349del 18p.V445_H450 delVGKKLHDelinframe. .0.23188406PD9599aPD9599b1745954530567589609GAAAGPIK3R1CCDS3993.1r.1415_1417de IAAAc.1373_1375del AAAp.K459delKDelinframe. .0.21818182PD4952aPD4952b1626485722567589622APIK3R1CCDS3993.1r.1428_1439del AUAUGAUAGAUUc.1386_1397del ATATGATAGATTp.D464_Y467 delDRLYDelinframe.0.32692308PD23567aPD23567b2331110214567589664TAPIK3R1CCDS3993.1r.1467+2u>ac.1425+2T>Ap.?Subess splice0.33.PD9575aPD9575b1854422025567591116TPIK3R1CCDS3993.1r.1752_1763del UAUCCAGCUGAGc.1710_1721del TATCCAGCTGAGp.1571_R574 dellQLRDelinframe. .0.17307692PD24195aPD24195b2397163484567591144APIK3R1CCDS3993.1r.1780_1787+2del UACUUGAUauc.1738_1745+2del TACTTGATgtp.?Deless splice.0.17391304PD22361aPD22361b242117270576035259GCPMS2CCDS5343.1r.915c>ac.809C>Gp.S270*Subnonsense0.27.PD13296aPD13296b13341079476106555250CAPRDM1CCDS5054.2r.2601c>ac.2367C>Ap.C789*Subnonsense0.15.PD6406aPD6406b2412234801868939479GAPREX2CCDS6201.1r.741a>ac.464G>Ap.R155QSubmissense0.077.PD8652a2PD8652b19694918171089653862GPTENENST 00000371953r.1518_1521+20del 24c.161_164+20del 24p.?Deless splice.0.15686275PD4872aPD4872b24221215631089685307TAPTENENST 00000371953r.1559u>ac202T>Ap.Y68NSubmissense0.14.PD11376aPD11376b15779107651089685314TGTAATPTENENST 00000371953r.1566+1_1566+4del auaac.209+1_209+4del ataap.?Deless splice. .0.425PD9589aPD9589b16009885491089692754TPTENENST 00000371953r.1611-15_1617del 22c.254-15_260del 22p.?Delframeshift.0.3030303PD6422aPD6422b23850927041089692904CTPTENENST 00000371953r.1745c>uc.388C>Tp.R130*Subnonsense0.37.PD23564aPD23564b24182926831089692904CTPTENENST 00000371953r.1745c>uc.388C>Tp.R130*Subnonsense0.21.PD10014aPD10014b18399086041089692905GAPTENENST 00000371953r.1746g>ac.389G>Ap.R130QSubmissense0.21.PD9694aPD9694b12108325071089692911GAPTENENST 00000371953r.1752g>ac.395G>Ap.G132DSubmissense0.26.PD4958aPD4958b16101560411089692984GPTENENST 00000371953r.1826_1835del GAAGUAAGGAc.469_478del GAAGTAAGGAp.E157fs"7Delframeshift.0.25925926PD5961aPD5961b22514020931089711873AGPTENENST 00000371953r.1850-2a>gc.493-2A>Gp.?Subess splice0.36.PD18257aPD18257b24282957891089711891GTPTENENST 00000371953r.1866a>uc.509G>Tp.S170ISubmissense0.29.PD11742aPD11742b23789243711089711952APTENENST 00000371953r.1928 1978del51c.571 621del51p.V191_S207 delVALLFHKM MFETIPMFSDelinframe.0.52631579PD5944aPD5944b24101499181089717609GAPTENENST 00000371953r.1992-1g>ac.635-1G>Ap.?Subess splice0.63.PD11368aPD11368b12797810871089717672CTPTENENST 00000371953r.2054c>uc.697C>Tp.R233*Subnonsense0.59.PD23564aPD23564b24182926871089717672CTPTENENST 00000371953r.2054c>uc.697C>Tp.R233*Subnonsense0.41.PD8965aPD8965b24099649371089717708CTPTENENST 00000371953r.2090c>uc.733C>Tp.Q245*Subnonsense0.39.PD11355aPD11355b17054044911089717739TAGAGTTCTPTENENST 00000371953r.2122_2128del AGAGUUCc.765_771del AGAGTTCp.E256fs*8Delframeshift. .0.3255814PD24320aPD24320b25604410911089717752CCAPTENENST 00000371953r.2134_2135insac.777_778insAp.Q261fs*37Insframeshift.0.52941176PD13422aPD13422b24944176931089717777GTPTENENST 00000371953r.2158+1g>uc.801+1G>Tp.?Subess splice0.33.PD10011aPD10011b25092359281089720650GCPTENENST 00000371953r.2159-1a>cc.802-1G>Cp.?Subess splice0.49.PD5953aPD5953b16568549501089720725TTGPTENENST 00000371953r.2233_2234insgc.876_877insGp.S294fs*4Insframeshift.0.6875PD4980aPD4980b22547803581089720741CTPTENENST 00000371953r.2249c>uc.892C>Tp.Q298*Subnonsense0.25.PD23567aPD23567b23304297691089720778APTENENST 00000371953r.2287_2306del 20c.930_949del 20p.N311fs*7Delframeshift.0.19354839PD3989aPD3989b15635500981089720798GTACTGPTENENST 00000371953r.2307_2310del UACUc.950_953del TACTp.T319fs*1Delframeshift.0.38461538PD6418aPD6418b17607165951089720798GTACTGPTENENST 00000371953r.2307_2310del UACUc.950_953del TACTp.T319fs*1Delframeshift.0.47916667PD7240aPD7240b25082273601089720798GTACTGPTENENST 00000371953r.2307_2310del UACUc.950_953del TACTp.T319fs*1Delframeshift.0.39473684PD11372aPD11372b15742320851089720804ACTTTAPTENENST 00000371953r.2313_2316del CUUUc.956_959del CTTTp.T319fs*24Delframeshift.0.51724138PD9575aPD9575b18539318061089720832CAAATCPTENENST 00000371953r.2341_2344del AAAUc.984_987del AAATp.N329fs"14Delframeshift.0.24137931PD6711a2PD6711b25035234351089720849APTENENST 00000371953r.2358_2383+23 del49c.1001_1026+23 del49p.?Deless splice.0.86666667PD24191aPD24191b23889921671089725036TPTENENST 00000371953r.2384-7_2419 del43c.1027-7_1062 del43p.?Deless splice.0.33333333PD6412aPD6412b17771059101348881488CAGCRB1CCDS31973.1r.349 350delAGc.211 212delAGp.R73fs"36Delframeshift.0.3442623PD13428aPD13428b24655038211348881513GTRB1CCDS31973.1r.373a>uc.235G>TpE79*Subnonsense0.61.PD13425aPD13425b13198640281348916759GTRB1CCDS31973.1r.427a>uc.289G>Tp.E97*Subnonsense0.43.PD4975aPD4975b24112042641348934234CARB1CCDS31973.1r.827c>ac.689C>Ap.S230*Subnonsense0.51.PD6414aPD6414b17526597221348934237CRB1CCDS31973.1 r.831_844del c.693_706delp.P232fs*4Delframeshift.0.14285714PD9702aPD9702b16346596311348934262TAGTATRB1CCDS31973.1r.856_856+3 delAauac.718_718+3 delAatap.?Deless splice.0.44444444PD24218aPD24218b24664764351348936786TRB1CCDS31973.1r.857-164_999 +25del332c.719-164_861 +25del332p.?Deless splice.0.44736842PD22357aPD22357b23151761871348941639CTTCRB1CCDS31973.1r.1088_1089delUUc.950_951delTTp.S318fs*1Delframeshift.0.46153846PD4844aPD4844b318333453841348941720CRB1CCDS31973.1 r.1169_1181 del c.1031_1043delp.D346fs"17Delframeshift.0.61538462PD11766aPD11766b25371754511348947540GARB1CCDS31973.1r.1266-1g>ac.1128-1G>Ap.?Subess splice0.4.PD7220aPD7220b22723042711348947596CTRB1CCDS31973.1r.1321c>uc.1183C>Tp.Q395*Subnonsense0.58.PD9568aPD9568b18530513341348951083ARB1CCDS31973.1r.1384_1435del52c.1246_1297del52p.K417fs*23Delframeshift.0.57777778PD24194aPD24194b24200999781348954320ATTARB1CCDS31973.1r.1580_1581delUUc.1442_1443delTTp.F482fs*10Delframeshift.0.27272727PD6722aPD6722b22571422651348955550CTRB1CCDS31973.1r.1804c>uc.1666C>Tp.R556*Subnonsense0.21.PD4956aPD4956b15209061741349030490GCRB1CCDS31973.1r.2098+5g>cc.1960+5G>Cp.?Subess splice0.61.PD6404aPD6404b20933028891349033844CTRB1CCDS31973.1r.2119c>uc.1981C>Tp.R661WSubmissense0.5.PD4980aPD4980b22547997591349033955ATRB1CCDS31973.1r.2230a>uc.2092A>Tp.R698WSubmissense0.21.PD5942aPD5942b22567880361349037866GCRB1CCDS31973.1r.2245-1a>cc.2107-1G>Cp.?Subess splice0.62.PD8965aPD8965b24099845411349037866GCRB1CCDS31973.1r.2245-1a>cc.2107-1G>Cp.?Subess splice0.52.PD7307aPD7307b20913376581349039505GCRB1CCDS31973.1r.2627+1g>cc.2489+1G>Cp.?Subess splice0.18.PD18031aPD18031b20333710181349050003TRB1CCDS31973.1r.2659-833_2801 +17del993c.2521-833_2663 +17del993p.?Deless splice.0.25490196PD9578aPD9578b2537070365349412898TCRHOACCDS2795.1r.510a>ac.125A>Gp.Y42CSubmissense0.34.PD11375aPD11375b1253100357349412973CTRHOACCDS2795.1r.435a>ac.50G>Ap.G17ESubmissense0.13.PD13604aPD13604b2266085534349412973CTRHOACCDS2795.1r.435a>ac.50G>Ap.G17ESubmissense0.29.PD9575aPD9575b18542791662136206899CTATTGTGGCRUNX1CCDS13639.1r.1059-9_1059-2 delccacaauac.614-9_614-2 delccacaatap.?Deless splice. .0.14545455PD11389aPD11389b16756956972136252984AATRUNX1CCDS13639.1r.822_823insac.377_378insAp.D126fs"12Insframeshift. .0.33333333PD11402aPD11402b16935146222136252994TTCCRUNX1CCDS13639.1r.812_813insggc.367_368insGGp.D123fs"11Insframeshift.0.23636364PD18775aPD18775b25364333302136253012TCRUNX1CCDS13639.1r.797-2a>ac.352-2A>Gp.?Subess splice0.21.PD9541aPD9541b1285838696347125824CASETD2CCDS2749.2r.5489g>uc.5446G>Tp.E1816*Subnonsense0.3.PD24320aPD24320b2560763499347129689CAGCSETD2CCDS2749.2r.5232_5233del CUc.5189_5190del CTp.S1730fs*1Delframeshift.0.32PD18748aPD18748b1823640599347158225GASETD2CCDS2749.2r.4517c>uc.4474C>Tp.R1492*Subnonsense0.22.PD4072aPD4072b2256085057347161957GCSETD2CCDS2749.2r.4212c>ac.4169C>Gp.S1390*Subnonsense0.16.PD11357aPD11357b1532379924347162506GAAGAGSETD2CCDS2749.2r.3659_3662del UCUUc.3616_3619del TCTTp.S1206fs*29Delframeshift.0.12195122PD9694aPD9694b12108987102198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp. K700ESubmissense0.15.PD13312aPD13312b13064955482198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp. K700ESubmissense0.5.PD9847aPD9847b13178283732198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp. K700ESubmissense0.53.PD13623aPD13623b15088682562198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp.K700ESubmissense0.19.PD13770aPD13770b18217768132198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp. K700ESubmissense0.13.PD4076aPD4076b18508292692198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp. K700ESubmissense0.16.PD18149aPD18149b20561267552198266834TCSF3B1CCDS33356.1r.2190a>ac.2098A>Gp.K700ESubmissense0.27.PD4965aPD4965b22555173822198266834TCSF3B1CCDS33356.1r.2190a>gc.2098A>Gp. K700ESubmissense0.26.PD3989aPD3989b22558437252198266834TCSF3B1CCDS33356.1r.2190a>gc.2098A>Gp. K700ESubmissense0.22.PD9572aPD9572b22636945532198266834TCSF3B1CCDS33356.1r.2190a>gc.2098A>Gp.K700ESubmissense0.26.PD9599aPD9599b24660453452198266834TCSF3B1CCDS33356.1r.2190a>gc.2098A>Gp. K700ESubmissense0.24.PD6711a2PD6711b25124498992198266834TCSF3B1CCDS33356.1r.2190a>gc.2098A>Gp. K700ESubmissense0.45.PD11384aPD11384b12069149762198267484GASF3B1CCDS33356.1r.1965c>uc.1873C>Tp.R625CSubmissense0.16.PD11337aPD11337b17203645931848584611CCATSMAD4CCDS11950.1r.1322_1323insauc.784_785insATp.N263fs*74Insframeshift.0.21621622PD13625aPD13625b18235094541848603116GTSMAD4CCDS11950.1r.1955a>uc.1417G>Tp.G473*Subnonsense0.68.PD4605aPD4605b22569946811911118599CTSMARCA4CCDS45971.1r.2307c>uc.2023C>Tp.Q675*Subnonsense0.23.PD9595aPD9595b16222693161911169548ASMARCA4CCDS45971.1r.4999_5015+8 del25c.4715_4731+8 del25p.?Deless splice.0.125PD23564aPD23564b2418257973116202812CTSPENCCDS164.1r.724c>uc.520C>Tp.R174*Subnonsense0.36.PD11762aPD11762b1333756018116255256GTSPENCCDS164.1r.2725g>uc.2521G>Tp.E841*Subnonsense0.13.PD11365aPD11365b1814193004116255882TTASPENCCDS164.1r.3351_3352insac.3147_3148insAp.11052fs*7Insframeshift.0.33333333PD11380aPD11380b1222739018116256282GTSPENCCDS164.1r.3751g>uc.3547G>Tp.E1183*Subnonsense0.095.PD14460aPD14460b2226070847116256320TTASPENCCDS164.1r.3789_3790insac.3585_3586insAp.D1198fs*4Insframeshift. .0.4516129PD24320aPD24320b2560364827116256320TTASPENCCDS164.1r.3789_3790insac.3585 3586insAp.D1198fs*4Insframeshift. .0.16666667PD4255aPD4255b1943569959116256666CSPENCCDS164.1r.4135_4136ins cuuauaauuaaaucuc.3931_3932ins CTTATGATTAAATCTp.D1313_S1314 ins*Insnonsense. .0.11111111PD13620aPD13620b2516032507116256965CAGCSPENCCDS164.1r.4435_4436delAGc.4231_4232delAGp.E1412fs*5Delframeshift.0.65PD9847aPD9847b1317762446116257359CTSPENCCDS164.1r.4828c>uc.4624C>Tp.R1542*Subnonsense0.75.PD9063aPD9063b2544622365116257743GTSPENCCDS164.1r.5212g>uc.5008G>Tp.E1670*Subnonsense0.19.PD13756aPD13756b2553711805116259452TGSPENCCDS164.1r.6921u>gc.6717T>Gp.Y2239*Subnonsense0.36.PD9004aPD9004b2277204768116259935TSPENCCDS164.1r.7405_7415del GACCUAAGCAAc.7201_7211del GACCTAAGCAAp.L2402fs"13Delframeshift.0.18918919PD11389aPD11389b1675195780116262679AACSPENCCDS164.1r.10148_10149inscc.9944_9945insCp.A3318fs*30Insframeshift.0.25641026PD5950aPD5950b1676912525X123164816TTASTAG2CCDS43990.1r.639_640insac.129_130insAp.G46fs*41Insframeshift.0.10714286PD8973aPD8973b2262405694X123197716CTSTAG2CCDS43990.1r.2350c>uc.1840C>Tp.R614*Subnonsense0.22.PD11741aPD11741b2495057080191219401CASTK11CCDS45896.1r.1568c>ac.453C>Ap.C151*Subnonsense0.15.PD7201aPD7201b226134018012115111972GATBX3CCDS9176.1r.2732c>uc.1768C>Tp.Q590*Subnonsense0.35.PD18776aPD18776b251700112612115112247AAGGTBX3CCDS9176.1r.2456_2457insccc.1492_1493insCCp.L498fs"135Insframeshift.0.15555556PD13427aPD13427b131544537212115112482CATBX3CCDS9176.1r.2222g>uc.1258G>Tp.E420*Subnonsense0.29.PD18188aPD18188b217921612212115112489GGATBX3CCDS9176.1r.2214_2215insuc.1250_1251insTp.A418fs*3Insframeshift.0.19565217PD9584aPD9584b227616440312115114115TTACTBX3CCDS9176.1r.2063+2_2063+3 insauc.1099+2_1099+3 insGTp.?Insess splice.0.26190476PD18049aPD18049b210660153512115114148CCGTBX3CCDS9176.1r.2032_2033inscc.1068_1069insCp.A357fs*18Insframeshift.0.33870968PD9541aPD9541b128579703412115114166GATBX3CCDS9176.1r.2015c>uc.1051C>Tp.Q351*Subnonsense0.24.PD11368aPD11368b155538921412115114215CTBX3CCDS9176.1r.1965_1966ins auaac.1001_1002ins ATGGp.T335fs*4Insframeshift.0.55555556PD7210aPD7210b174749209012115114232GTBX3CCDS9176.1r.1948_1949insaagac.984_985insAAGAp.H329fs*10Insframeshift.0.22222222PD18756aPD18756b253380014112115115404TTTCTBX3CCDS9176.1r.1885_1886insgac.921_922insGAp.N308fs"16Insframeshift.0.17307692PD5937aPD5937b158725317412115117307TATTBX3CCDS9176.1r.1828+2deluc.864+2deltp.?Deless splice.0.23943662PD11816aPD11816b166458395112115118733GGTTBX3CCDS9176.1r.1571_1572insac.607_608insAp.T203fs*24Insframeshift.0.19298246PD9009aPD9009b214847824712115118888TAAAATGTTBX3CCDS9176.1r.1411_1416del CAUUUUc.447_452del CATTTTp.Y149_L151 delins*Delnonsense.0.12068966PD11766aPD11766b25372722764106190819GATET2CCDS47120.1r.4483a>ac.4097G>Ap.R1366HSubmissense0.23.PD7249aPD7249b1253959948177573996ACTP53CCDS11118.1r.1221u>ac.1031T>Gp.L344RSubmissense0.73.PD3905aPD3905b2543711902177573997GCTGTP53CCDS11118.1r.1218_1219delAGc.1028_1029delAGp.E343fs*3Delframeshift.0.16666667PD8982aPD8982b1517528762177574002CGCTP53CCDS11118.1r.1214delCc.1024delCp.R342fs*3Delframeshift.0.5PD11379aPD11379b2415428980177574002CGTP53CCDS11118.1r.1215a>cc.1025G>Cp.R342PSubmissense0.65.PD18022aPD18022b2512547392177574002CGTP53CCDS11118.1r.1215a>cc.1025G>Cp.R342PSubmissense0.23.PD22359aPD22359b2417462675177574003GATP53CCDS11118.1r.1214c>uc.1024C>Tp.R342*Subnonsense0.26.PD24206aPD24206b2400100644177574006ATP53CCDS11118.1r.1190_1210del21c.1000_1020del21p.G334_M340 delGRERFEMDelinframe.0.22727273PD18017aPD18017b2510512182177574017CGCTCACGCTP53CCDS11118.1r.1193_1199del CGUGAGCc.1003_1009del CGTGAGCp.R335fs"8Delframeshift.0.3PD5947aPD5947b2390580769177574018GATP53CCDS11118.1r.1199c>uc.1009C>Tp.R337CSubmissense0.32.PD24224aPD24224b2503363536177574018GATP53CCDS11118.1r.1199c>uc.1009C>Tp.R337CSubmissense0.32.PD5948aPD5948b1934523985177574026CCCATP53CCDS11118.1r.1190_1191insugc.1000 1001insTGp.G334fs*12Insframeshift.0.61764706PD5942aPD5942b2256811525177574034CGTP53CCDS11118.1r.1184-1a>cc.994-1G>Cp.?Subess splice0.78.PD7206aPD7206b1775562698177576827TTP53CCDS11118.1r.1183+1_1183 +25del25c.993+1_993 +25del25p.?Deless splice.0.23809524PD8652a2PD8652b2273625752177576851ATTP53CCDS11118.1r.1183+2u>ac.993+2T>Ap.?Subess splice0.33.PD22363aPD22363b2319670515177576852CGTP53CCDS11118.1r.1183+1g>cc993+1G>Cp.?Subess splice0.52.PD23578aPD23578b2416581267177576852CGTP53CCDS11118.1r.1183+1g>cc993+1G>Cp.?Subess splice0.35.PD4199aPD4199b2539990019177576852CTTP53CCDS11118.1r.1183+1g>ac.993+1G>Ap.?Subess splice0.43.PD4967aPD4967b2246389907177576855GATP53CCDS11118.1r.1181c>uc.991C>Tp.Q331*Subnonsense0.18.PD7069aPD7069b2511655012177576855GATP53CCDS11118.1r.1181c>uc.991C>Tp.Q331*Subnonsense0.089.PD4836aPD4836b1473663973177576862GAGTP53CCDS11118.1r.1173delUc.983delTp.F328fs*17Delframeshift.0.36PD9604aPD9604b2245824381177576865ATTP53CCDS11118.1r.1171u>ac.981T>Ap.Y327*Subnonsense0.64.PD7426aPD7426b1852764028177576873CATP53CCDS11118.1r.1163g>uc.973G>Tp.G325*Subnonsense0.33.PD9760aPD9760b1292097859177576885TATP53CCDS11118.1r.1151a>uc961A>Tp.K321*Subnonsense0.61.PD24329aPD24329b2576106260177576897GATP53CCDS11118.1r.1139c>uc.949C>Tp.Q317*Subnonsense0.63.PD7250aPD7250b1589180597177577005TTP53CCDS11118.1r.1109+2_1109 +13deluaagcaag caggc919+2_919 +13deltaagcaag caggp.?Deless splice.0.33333333PD11751aPD11751b1337595770177577018CGTP53CCDS11118.1r.1109+1g>cc.919+1G>Cp.?Subess splice0.72.PD11398aPD11398b1657932366177577049GTP53CCDS11118.1r.1078_1079ins ucacc.888_889ins TCACp.H297fs*10Insframeshift.0.32352941PD24216aPD24216b2483877659177577060CCTCTP53CCDS11118.1r.1066_1067delAGc.876 877delAGp.E294fs"11Delframeshift.0.28571429PD9579aPD9579b2272673262177577085CTTP53CCDS11118.1r.1043g>ac.853G>Ap.E285KSubmissense0.17.PD18251aPD18251b2458814773177577085CTTP53CCDS11118.1r.1043g>ac.853G>Ap.E285KSubmissense0.62.PD5944aPD5944b2410184836177577094GATP53CCDS11118.1r.1034c>uc.844C>Tp.R282WSubmissense0.34.PD6410aPD6410b2411423186177577094GATP53CCDS11118.1r.1034c>uc.844C>Tp.R282WSubmissense0.28.PD7067aPD7067b1778224942177577095GTCTCTCGTP53CCDS11118.1r.1027_1032del GAGAGAc.837_842del GAGAGAp.D281_R282 delDRDelinframe.0.35897436PD7304aPD7304b2174762912177577096TCTP53CCDS11118.1r.1032a>ac.842A>Gp.D281GSubmissense0.16.PD13163aPD13163b2184412669177577097CGTP53CCDS11118.1r.1031g>cc.841G>Cp.D281HSubmissense0.69.PD8609aPD8609b2409474071177577099CTTP53CCDS11118.1r.1029g>ac.839G>Ap. R280KSubmissense0.33.PD24337aPD24337b2550430644177577099CTTP53CCDS11118.1r.1029g>ac.839G>Ap. R280KSubmissense0.75.PD13166aPD13166b2407228871177577105GATP53CCDS11118.1r.1023c>uc.833C>Tp.P278LSubmissense0.56.PD8832aPD8832b1586407525177577111GCACGTP53CCDS11118.1r.1014_1016del GUGc.824_826del GTGp.C275_A276 delinsSDelcomplex sub. .0.42424242PD4847aPD4847b21945409374177577113ATP53CCDS11118.1 r.1014_1015ins c.824_825insp.C275_A276 insFEVRVCInsinframe.0.07272727PD18031aPD18031b2300800247177577117ACTP53CCDS11118.1r.1011u>gc.821T>Gp.V274GSubmissense0.19.PD6727bPD6727a1227587250177577120CTTP53CCDS11118.1r.1008g>ac.818G>Ap.R273HSubmissense0.47.PD8619aPD8619b1535642293177577120CTTP53CCDS11118.1r.1008g>ac.818G>Ap.R273HSubmissense0.46.PD5934aPD5934b2253330240177577120CTTP53CCDS11118.1r.1008g>ac.818G>Ap.R273HSubmissense0.62.PD13603aPD13603b2268092002177577120CTTP53CCDS11118.1r.1008g>ac.818G>Ap.R273HSubmissense0.59.PD22366aPD22366b2319443612177577120CTTP53CCDS11118.1r.1008g>ac.818G>Ap.R273HSubmissense0.39.PD24196aPD24196b2385366340177577120CATP53CCDS11118.1r.1008g>uc.818G>Tp.R273LSubmissense0.39.PD8979aPD8979b1212077867177577121GATP53CCDS11118.1r.1007c>uc.817C>Tp.R273CSubmissense0.14.PD9752aPD9752b1222394733177577121GATP53CCDS11118.1r.1007c>uc.817C>Tp.R273CSubmissense0.47.PD18050aPD18050b2187550665177577121GTTP53CCDS11118.1r.1007c>ac.817C>Ap.R273SSubmissense0.38.PD8621aPD8621b2245984165177577121GCTP53CCDS11118.1r.1007c>ac.817C>Gp.R273GSubmissense0.66.PD18020aPD18020b2510166985177577121GATP53CCDS11118.1r.1007c>uc.817C>Tp.R273CSubmissense0.5.PD22355aPD22355b2309648018177577124CTTP53CCDS11118.1r.1004a>ac.814G>Ap.V272MSubmissense0.78.PD13418aPD13418b1517087384177577127CTTP53CCDS11118.1r.1001g>ac.811G>Ap.E271KSubmissense0.89.PD8830aPD8830b2262554954177577141CTTP53CCDS11118.1r.987g>ac.797G>Ap.G266ESubmissense0.5.PD11393aPD11393b2449969560177577151TACCTTP53CCDS11118.1r.974_976del GGUc.784_786del GGTp.G262delGDelinframe.0.4PD22357aPD22357b2319549354177577156CTTP53CCDS11118.1r.973-1g>ac.783-1G>Ap.?Subess splice0.72.PD5951aPD5951b2259719426177577498CATP53CCDS11118.1r.972+1g>uc.782+1G>Tp.?Subess splice0.44.PD22360aPD22360b2322698493177577498CGTP53CCDS11118.1r.972+1g>cc.782+1G>Cp.?Subess splice0.28.PD24201aPD24201b2398725893177577501GTP53CCDS11118.1r.947 969del23c.757 779del23p.T253fs*3Delframeshift.0.45PD24326aPD24326b2536893812177577505TATP53CCDS11118.1r.966a>uc.776A>Tp.D259VSubmissense0.67.PD8965aPD8965b2410005573177577507TGTP53CCDS11118.1r.964a>cc.774A>Cp.E258DSubmissense0.57.PD13299aPD13299b1579781138177577514GTGAGTP53CCDS11118.1r.954_956del UCAc.764_766del TCAp.I255dellDelinframe.0.55555556PD10014aPD10014b1839956703177577517AGTP53CCDS11118.1r.954u>cc.764T>Cp.I255TSubmissense0.68.PD6729a2PD6729a1968312604177577526AGTP53CCDS11118.1r.945u>cc.755T>Cp.L252PSubmissense0.69.PD4962aPD4962b2496023034177577538CTTP53CCDS11118.1r.933g>ac.743G>Ap.R248QSubmissense0.21.PD24314aPD24314b2505871093177577538CTTP53CCDS11118.1r.933g>ac.743G>Ap.R248QSubmissense0.47.PD14435aPD14435b2567661196177577538CTTP53CCDS11118.1r.933g>ac.743G>Ap.R248QSubmissense0.76.PD6413aPD6413b.177577538CTTP53CCDS11118.1r.933g>ac.743G>Ap.R248QSubmissense0.2.PD3890aPD3890b2068115666177577539GATP53CCDS11118.1r.932c>uc.742C>Tp.R248WSubmissense0.57.PD13167aPD13167b2151863955177577539GATP53CCDS11118.1r.932c>uc.742C>Tp.R248WSubmissense0.5.PD18049aPD18049b2406509627177577539GATP53CCDS11118.1r.932c>uc.742C>Tp.R248WSubmissense0.17.PD13622aPD13622b1697657316177577544ATP53CCDS11118.1 r.912_926del c.722_736delp.S241_M246 delinsLDelcomplex sub.0.44827586PD22361aPD22361b2421119494177577547CATP53CCDS11118.1r.924a>uc.734G>Tp.G245VSubmissense0.39.PD4980aPD4980b2254816221177577548CATP53CCDS11118.1r.923g>uc.733G>Tp.G245CSubmissense0.52.PD11742aPD11742b2380187734177577548CTTP53CCDS11118.1r.923g>ac.733G>Ap.G245SSubmissense0.6.PD8969aPD8969b2409648540177577548CTTP53CCDS11118.1r.923g>ac.733G>Ap.G245SSubmissense0.32.PD18771aPD18771b2479176762177577550CTTP53CCDS11118.1r.921g>ac.731G>Ap.G244DSubmissense0.31.PD23577aPD23577b2386334790177577557AGATP53CCDS11118.1r.913delCc.723delCp.C242fs*5Delframeshift.0.68421053PD11345aPD11345b2184733461177577559GATP53CCDS11118.1r.912c>uc.722C>Tp.S241FSubmissense0.77.PD11341aPD11341b2414167657177577559GATP53CCDS11118.1r.912c>uc.722C>Tp.S241FSubmissense0.11.PD6046aPD6046b2249173589177577560ACTP53CCDS11118.1r.911u>ac.721T>Gp.S241ASubmissense0.55.PD14454aPD14454b2493786496177577560ATTP53CCDS11118.1r.911u>ac.721T>Ap.S241TSubmissense0.27.PD9568aPD9568b1853706344177577567ATTP53CCDS11118.1r.904u>ac.714T>Ap.C238*Subnonsense0.67.PD4847aPD4847b22411638755177577568CTTP53CCDS11118.1r.903g>ac.713G>Ap.C238YSubmissense0.21.PD22364aPD22364b2416920919177577568CATP53CCDS11118.1r.903g>uc.713G>Tp.C238FSubmissense0.7.PD9592aPD9592b1398972192177577570CATP53CCDS11118.1r.901g>uc.711G>Tp.M237ISubmissense0.42.PD11346aPD11346b2162589007177577570CTTP53CCDS11118.1r.901g>ac.711G>Ap.M237ISubmissense0.75.PD9599aPD9599b1745598719177577572TGTATTP53CCDS11118.1r.896_898del UACc.706_708del TACp.Y236delYDelinframe.0.64705882PD7316aPD7316b1403020350177577579GTTP53CCDS11118.1r.892c>ac.702C>Ap.Y234*Subnonsense0.32.PD4976aPD4976b2254484393177577580TCTP53CCDS11118.1r.891a>gc.701A>Gp.Y234CSubmissense0.85.PD6732bPD6732a1227771704177577581ATTP53CCDS11118.1r.890u>ac.700T>Ap.Y234NSubmissense0.39.PD18048aPD18048b2133730644177577609CATP53CCDS11118.1r.863-1g>uc.673-1G>Tp.?Subess splice0.56.PD8981aPD8981b1204887437177578175ATTP53CCDS11118.1r.862+2u>ac.672+2T>Ap.?Subess splice0.58.PD8964aPD8964b2261030290177578176CATP53CCDS11118.1r.862+1g>uc.672+1G>Tp.?Subess splice0.54.PD11344aPD11344b2184229028177578189ACTP53CCDS11118.1r.850u>ac.660T>Gp.Y220*Subnonsense0.33.PD8980aPD8980b1204303771177578190TCTP53CCDS11118.1r.849a>ac.659A>Gp.Y220CSubmissense0.61.PD13630aPD13630b1818129390177578190TCTP53CCDS11118.1r.849a>ac.659A>Gp.Y220CSubmissense0.3.PD4109aPD4109b1822277093177578190TCTP53CCDS11118.1r.849a>ac.659A>Gp.Y220CSubmissense0.41.PD24192aPD24192b2388124017177578190TCTP53CCDS11118.1r.849a>ac.659A>Gp.Y220CSubmissense0.93.PD24327aPD24327b2575724294177578190TCTP53CCDS11118.1r.849a>ac.659A>Gp.Y220CSubmissense0.37.PD24308aPD24308b2505969607177578191ATTP53CCDS11118.1r.848u>ac.658T>Ap.Y220NSubmissense0.64.PD11326aPD11326b1931258472177578198CACCACACTACTP53CCDS11118.1r.832_840del UAGUGUGGUc.642_650del TAGTGTGGTp.H214_V217 delinsQDelcomplex sub.0.5PD11349aPD11349b2169010015177578203CTTP53CCDS11118.1r.836g>ac.646G>Ap.V216MSubmissense0.45.PD24223aPD24223b2472825740177578203CTTP53CCDS11118.1r.836g>ac.646G>Ap.V216MSubmissense0.5.PD9595aPD9595b2244652865177578211CATP53CCDS11118.1r.828g>uc.638G>Tp.R213LSubmissense0.69.PD5950aPD5950b1228192510177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.22.PD4005aPD4005b2068790858177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.48.PD6730bPD6730b22271992479177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.25.PD7428aPD7428b2292293260177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.76.PD7066aPD7066b2302187235177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.14.PD23563aPD23563b2353151930177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.26.PD8660a2PD8660b2408902605177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.73.PD4975aPD4975b2411225612177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.27.PD4874aPD4874b2412354020177578212GATP53CCDS11118.1r.827c>uc.637C>Tp.R213*Subnonsense0.51.PD7248aPD7248b1757726770177578221TTCTTP53CCDS11118.1r.816_817del GAc.626_627del GAp. R209fs*6Delframeshift. .0.44117647PD9575aPD9575b1854124090177578221TTCTTP53CCDS11118.1r.816_817del GAc.626_627del GAp.R209fs*6Delframeshift.0.23809524PD7344aPD7344b2296604825177578224TATP53CCDS11118.1r.815a>uc.625A>Tp.R209*Subnonsense0.097.PD8997aPD8997b2091620382177578236AGTP53CCDS11118.1r.803u>cc.613T>Cp.Y205HSubmissense0.36.PD23554aPD23554b2342130322177578236ATTP53CCDS11118.1r.803u>ac.613T>Ap.Y205NSubmissense0.54.PD9585aPD9585b1966155039177578249AATTP53CCDS11118.1r.789_790insac.599_600insAp.N200fs*9Insframeshift.0.46428571PD4107aPD4107b1756932597177578262CGCTP53CCDS11118.1r.776delCc.586delCp. R196fs*51Delframeshift.0.52941176PD5925aPD5925b1208711553177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.25.PD6047aPD6047b1226403934177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.84.PD13297aPD13297b1520069071177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.89.PD6412aPD6412b2258611747177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.48.PD24208aPD24208b2385277030177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.72.PD7211aPD7211b2409855477177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.47.PD24318aPD24318b2566344757177578263GATP53CCDS11118.1r.776c>uc.586C>Tp.R196*Subnonsense0.75.PD7217aPD7217b2258787226177578265AGTP53CCDS11118.1r.774u>cc.584T>Cp.I195TSubmissense0.14.PD13425aPD13425b1319882454177578268ACTP53CCDS11118.1r.771u>ac.581T>Gp.L194RSubmissense0.5.PD11327aPD11327b2511287788177578268ACTP53CCDS11118.1r.771u>gc.581T>Gp.L194RSubmissense0.12.PD9696aPD9696b1226130073177578271TCTP53CCDS11118.1r.768a>gc.578A>Gp.H193RSubmissense0.14.PD7321aPD7321b2244809150177578271TCTP53CCDS11118.1r.768a>gc.578A>Gp.H193RSubmissense0.31.PD6722aPD6722b2257181026177578271TCTP53CCDS11118.1r.768a>gc.578A>Gp.H193RSubmissense0.13.PD11743aPD11743b1822830637177578275GATP53CCDS11118.1r.764c>uc.574C>Tp.Q192*Subnonsense0.41.PD4826aPD4826b2259893103177578275GATP53CCDS11118.1r.764c>uc.574C>Tp.Q192*Subnonsense0.32.PD7240aPD7240b2509079916177578290CTTP53CCDS11118.1r.750-1g>ac560-1 G>Ap.?Subess splice0.42.PD10011aPD10011b2509280078177578370CTTP53CCDS11118.1r.749+1g>ac.559+1G>Ap.?Subess splice0.43.PD24202aPD24202b2391624902177578375GCTATGTP53CCDS11118.1r.741_744del AUAGc.551_554del ATAGp.D184fs*62Delframeshift.0.375PD4604aPD4604b2257880104177578382GCTP53CCDS11118.1r.738c>gc.548C>Gp.S183*Subnonsense0.6.PD9759aPD9759b1316897443177578384GCTP53CCDS11118.1r.736c>gc.546C>Gp.C182WSubmissense0.31.PD4875aPD4875b2245658673177578388CGTP53CCDS11118.1r.732g>cc.542G>Cp.R181PSubmissense0.35.PD8978aPD8978b1245128967177578394TCTP53CCDS11118.1r.726a>gc.536A>Gp.H179RSubmissense0.66.PD9571aPD9571b1856217761177578394TCTP53CCDS11118.1r.726a>gc.536A>Gp.H179RSubmissense0.88.PD4255aPD4255b2255363349177578394TCTP53CCDS11118.1r.726a>gc.536A>Gp.H179RSubmissense0.56.PD4968aPD4968b2258225638177578394TCTP53CCDS11118.1r.726a>gc.536A>Gp.H179RSubmissense0.36.PD13311aPD13311b2512181886177578394TCTP53CCDS11118.1r.726a>gc.536A>Gp.H179RSubmissense0.19.PD24225aPD24225b.177578394TCTP53CCDS11118.1r.726a>gc.536A>Gp.H179RSubmissense0.25.PD9009aPD9009b2406843420177578398GCTP53CCDS11118.1r.722c>gc.532C>Gp.H178DSubmissense0.21.PD24194aPD24194b2537519866177578402GCTP53CCDS11118.1r.718c>gc.528C>Gp.C176WSubmissense0.19.PD6731a2PD6731a1969271932177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.21.PD18024aPD18024b2056732810177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.24.PD6404aPD6404b2093329831177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.39.PD9576aPD9576b2094487059177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.41.PD13609aPD13609b2163055289177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.45.PD18037aPD18037b2306349256177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.24.PD23566aPD23566b2348373374177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.47.PD6728bPD6728a2409342084177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.56.PD23574aPD23574b2420761347177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.38.PD11750aPD11750b2494223506177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.27.PD24182aPD24182b2505756053177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.27.PD6409aPD6409b.177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.11.PD24221aPD24221b. .177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.23.PD6405aPD6405b. .177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.74.PD24191aPD24191b.177578406CTTP53CCDS11118.1r.714g>ac.524G>Ap.R175HSubmissense0.85.PD9702aPD9702b1227965555177578407GCTP53CCDS11118.1r.713c>ac.523C>Gp.R175GSubmissense0.53.PD4605aPD4605b2256988490177578416CATP53CCDS11118.1r.704a>uc.514G>Tp.V172FSubmissense0.4.PD8984aPD8984b1544463690177578420CGCTP53CCDS11118.1r.699delCc.509delCp.T170fs*4Delframeshift.0.44444444PD24215aPD24215b2495484740177578434ACATP53CCDS11118.1r.685delGc.495delGp.Q165fs*5Delframeshift.0.5625PD11745aPD11745b2460099537177578437GATP53CCDS11118.1r.683c>uc.493C>Tp.Q165*Subnonsense0.35.PD18046aPD18046b2138030829177578440TATP53CCDS11118.1r.680a>uc.490A>Tp.K164*Subnonsense0.73.PD6406aPD6406b1707441109177578441TP53CCDS11118.1 r.664_678del c.474 488delp.A159fs*8Complexframeshift.0.23076923PD6411aPD6411b2246959717177578442TCTP53CCDS11118.1r.678a>ac.488A>Gp.Y163CSubmissense0.22.PD9002aPD9002b2464183187177578442TCTP53CCDS11118.1r.678a>ac.488A>Gp.Y163CSubmissense0.77.PD9539aPD9539b2536705007177578442TCTP53CCDS11118.1r.678a>ac.488A>Gp.Y163CSubmissense0.74.PD24220aPD24220b2575420859177578442TCTP53CCDS11118.1r.678a>ac.488A>Gp.Y163CSubmissense0.82.PD14471aPD14471b2047432076177578454GATP53CCDS11118.1r.666c>uc.476C>Tp.A159VSubmissense0.76.PD4841aPD4841b2257630334177578463CGTP53CCDS11118.1r.657g>cc.467G>Cp.R156PSubmissense0.83.PD13627aPD13627b1512414345177578470CTP53CCDS11118.1 r.637_649del c.447_459delp.T150fs*16Delframeshift.0.38095238PD4833aPD4833b1938400760177578474CCGTP53CCDS11118.1r.645_646inscc.455_456insCp.P153fs*28Insframeshift.0.29545455PD4971aPD4971b2260231437177578479GATP53CCDS11118.1r.641c>uc.451C>Tp.P151SSubmissense0.57.PD23559aPD23559b2538286233177578479GATP53CCDS11118.1r.641c>uc.451C>Tp.P151SSubmissense0.36.PD5945aPD5945b2252057034177578492CTTP53CCDS11118.1r.628a>ac.438G>Ap.W146*Subnonsense0.86.PD8612aPD8612b1576288285177578496AGCATP53CCDS11118.1r.622_623del GCc.432_433del GCp.Q144fs*4Delframeshift.0.34883721PD24193aPD24193b2398137732177578505GTTP53CCDS11118.1r.615c>ac.425C>Ap.P142HSubmissense0.21.PD13428aPD13428b1513322036177578506GGCTP53CCDS11118.1r.613 614insgc.423 424insGp.P142fs*7Insframeshift.0.61111111PD13298aPD13298b1216451427177578508CTTP53CCDS11118.1r.612a>ac.422G>Ap.C141YSubmissense0.7.PD4252aPD4252b.177578515TGTTP53CCDS11118.1c.414delCp.K139fs*31DelFrameshift del.PD8615aPD8615b1838010423177578526CTTP53CCDS11118.1r.594a>ac.404G>Ap.C135YSubmissense0.25.PD24219aPD24219b2576231336177578532ACTP53CCDS11118.1r.588u>ac.398T>Gp.M133RSubmissense0.75.PD7307aPD7307b2091365184177578535TCTP53CCDS11118.1r.585a>ac.395A>Gp.K132RSubmissense0.22.PD7220aPD7220b2272325837177578535TCTP53CCDS11118.1r.585a>ac.395A>Gp.K132RSubmissense0.57.PD24197aPD24197b2417229886177578535TCTP53CCDS11118.1r.585a>ac.395A>Gp.K132RSubmissense0.33.PD23560aPD23560b2342518992177578555CGTP53CCDS11118.1r.566-1a>cc.376-1G>Cp.?Subess splice0.16.PD13608aPD13608b2407839957177578556TCTP53CCDS11118.1r.566-2a>ac.376-2A>Gp.?Subess splice0.39.PD11752aPD11752b1749495884177579310ACATP53CCDS11118.1r.565+1delgc.375+1 delgp.?Deless splice.0.40425532PD5935aPD5935b1405472204177579313GCTP53CCDS11118.1r.564c>ac.374C>Gp.T125RSubmissense0.55.PD9004aPD9004b2277469774177579320TCATTP53CCDS11118.1r.555_556delUGc.365_366delTGp.V122fs"26Delframeshift.0.4PD8611aPD8611b1770848368177579335TCTTP53CCDS11118.1r.541delGc.351 delGp.T118fs*5Delframeshift.0.11627907PD4192aPD4192b2556540440177579344GTP53CCDS11118.1 r.520_532del c.330_342delp.L111fs*8Delframeshift.0.27586207PD4956aPD4956b1623736521177579358CGCTP53CCDS11118.1r.518delCc.328delCp.R110fs*13Delframeshift.0.5PD4844aPD4844b31833425927177579358CGCTP53CCDS11118.1r.518delCc.328delCp.R110fs*13Delframeshift.0.74285714PD9064aPD9064b2304124707177579359GGAAACCGTP53CCDS11118.1r.512_517del GGUUUCc.322_327del GGTTTCp.G108_F109 delGFDelinframe.0.31428571PD14437aPD14437b1844212716177579377GATP53CCDS11118.1r.500c>uc.310C>Tp.Q104*Subnonsense0.32.PD9464aPD9464b1800722614177579382GTGTP53CCDS11118.1r.494delAc.304delAp.T102fs*21Delframeshift.0.53846154PD6733bPD6733a1228717176177579389GATP53CCDS11118.1r.488c>uc.298C>Tp.Q100*Subnonsense0.21.PD6043aPD6043b1738551249177579391GTP53CCDS11118.1r.430_485del56c.240_295del56p.T81fs*49Delframeshift.0.35294118PD7238aPD7238b1599558980177579395GGACAGTP53CCDS11118.1r.478_481del UGUCc.288_291del TGTCp.V97fs*25Delframeshift.0.6PD11748aPD11748b1653083632177579397ATP53CCDS11118.1r.463_479del17c.273_289del17p.W91fs*52Delframeshift.0.17073171PD6415aPD6415b1856629336177579405TTGTP53CCDS11118.1r.471_472inscc.281_282insCp.S95fs*54Insframeshift.0.28571429PD23565aPD23565b2417338376177579415CTTP53CCDS11118.1r.462a>ac.272G>Ap.W91*Subnonsense0.38.PD6719aPD6719b1772470964177579470CGCTP53CCDS11118.1r.406delCc.216delCp.V73fs*50Delframeshift.0.15625PD11462aPD11462b2171152117177579470CGCTP53CCDS11118.1r.406delCc.216delCp.V73fs*50Delframeshift.0.52631579PD24333aPD24333b2548020384177579470CCGTP53CCDS11118.1r.406 407inscc.216 217insCp.V73fs*76Insframeshift.0.57142857PD23562aPD23562b2335015342177579486TTGTP53CCDS11118.1r.390 391inscc.200 _201insCp.E68fs*81Insframeshift.0.69230769PD10010aPD10010b1257633997177579494TATP53CCDS11118.1r.383a>uc.193A>Tp.R65*Subnonsense0.8.PD14453aPD14453b1529376150177579494TGTTP53CCDS11118.1r.382delCc.192delCp.R65fs*58Delframeshift.0.31578947PD23567aPD23567b2330590459177579525GAGTP53CCDS11118.1r.351delUc.161delTp.F54fs*69Delframeshift.0.12PD4086aPD4086b1515036285177579528CTTP53CCDS11118.1r.349g>ac.159G>Ap.W53*Subnonsense0.57.PD7215aPD7215b2253910115177579529CTTP53CCDS11118.1r.348g>ac.158G>Ap.W53*Subnonsense0.27.PD5932aPD5932b1936022652177579534TTCAATTP53CCDS11118.1r.339_342del UUGAc.149_152del TTGAp.I50fs*72Delframeshift.0.3030303PD8617aPD8617b1523116285X40994073TGTUSP9XCCDS43930.1r.1052delGc.419delGp.W140fs*1Delframeshift.0.26666667PD6412aPD6412b1777921119X41043647CAGGTCUSP9XCCDS43930.1r.3913-2_3914 delaaGUc.3280-2_3281 delaaGTp.?Deless splice.0.3PD11367aPD11367b2551397719X41057947TCAAATUSP9XCCDS43930.1r.5181_5184del CAAAc.4548_4551del CAAAp.Q1518fs*1Delframeshift.0.54166667PD23564aPD23564b2338038178X41075671CCTUSP9XCCDS43930.1r.6484_6485insuc.5851_5852insTp.Y1953fs*2Insframeshift.0.24719101PD4972aPD4972b15722921012229191600AGAXBP1CCDS13847.1r.792delCc.719delCp.P240fs*20Delframeshift.0.44736842PD4606aPD4606b17432170892229191658GXBP1CCDS13847.1r.734_735ins aaauacccuucc.661_662ins AAATGCCCTTCp.P221fs*43Insframeshift.0.125PD13604aPD13604b22655686952229192037CTGCXBP1CCDS13847.1r.668_669delCAc.595_596delCAp.Q199fs*187Delframeshift.0.16071429PD11394aPD11394b16113260582229192046AAGAXBP1CCDS13847.1r.659_660delCUc.586_587delCTp.L196fs*190Delframeshift.0.39130435PD11396aPD11396b15986275921469256797AAGZFP36L1CCDS9791.1r.2267_2268inscc.469_470insCp.L157fs*24Insframeshift.0.44444444PD13605aPD13605b21321888261469257086TGTZFP36L1CCDS9791.1r.1978delCc.180delCp.K61fs*19Delframeshift.0.44444444PD23570aPD23570b24178882131089624274TAPTENENST00000371953r.1405u>ac.48T>Ap.Y16*Subnonsense0.4.PD8615aPD8615b18302009301089624294TTAPTENENST00000371953r.1425_1426insac.68_69insAp.D24fs"20Insframeshift.0.31034483PD24190aPD24190b23937012371089624265AAGGAGATAPTENENST00000371953r.1397_1403del AGGAGAUc.40_46del AGGAGATp.R14fs*8Delframeshift.0.4PD11361aPD11361b1696257319556167838AACMAP3K1CCDS43318.1r.1403_1404inscc.1403_1404insCp.H469fs"12Insframeshift.0.19354839PD11361aPD11361b1696257321556177998CMAP3K1CCDS43318.1r.2972_2987del16c.2972_2987del16p.S992fs*85Delframeshift.0.18181818PD7221aPD7221b22511202592057484420CTGNASCCDS46622.1r.2533c>uc.2530C>Tp.R844CSubmissense0.42.PD11366aPD11366b15081950512057484420CTGNASCCDS46622.1r.2533c>uc.2530C>Tp.R844CSubmissense0.35. Table 7B Sample Tumour name Gene Effect PD11338PD11338aDNMT3AHDPD14467PD14467aDNMT3AHDPD13296PD13296aPIK3CAampPD22355PD22355aPIK3CAampPD7428PD7428aPIK3CAampPD8611PD8611aPIK3CAampPD13428PD13428aPIK3CAampPD5945PD5945aPIK3CAampPD6411PD6411aPIK3CAampPD24224PD24224aPIK3CAampPD11327PD11327aPIK3CAampPD8980PD8980aPIK3CAampPD5950PD5950aPIK3CAampPD23562PD23562aPIK3CAampPD24202PD24202aPIK3CAampPD22366PD22366aPIK3CAampPD23558PD23558aPIK3CAampPD11349PD11349aPDGFRAampPD23560PD23560aPDGFRAampPD7428PD7428aPDGFRAampPD6410PD6410aPDGFRAampPD6684PD6684aMAP3K1HDPD18020PD18020aMAP3K1HDPD22036PD22036aCCND3ampPD7428PD7428aCCND3ampPD4874PD4874aCCND3ampPD11327PD11327aCCND3ampPD5950PD5950aCCND3ampPD3905PD3905aCCND3ampPD6732PD6732bCCND3ampPD18037PD18037aCCND3ampPD23554PD23554aCCND3ampPD5942PD5942aCCND3ampPD24318PD24318aCCND3ampPD24308PD24308aCCND3ampPD7067PD7067aCCND3ampPD4264PD4264aCCND3ampPD22251PD22251aCCND3ampPD5932PD5932aCCND3ampPD5942PD5942aESR1ampPD13425PD13425aESR1ampPD24199PD24199aESR1ampPD24216PD24216aESR1ampPD6416PD6416aEGFRampPD24314PD24314aEGFRampPD24308PD24308aEGFRampPD24326PD24326aEGFRampPD11766PD11766aEGFRampPD22361PD22361aEGFRampPD24201PD24201aCDK6ampPD6043PD6043aCDK6ampPD14453PD14453aCDK6ampPD4605PD4605aCDK6ampPD9464PD9464aCDK6ampPD11751PD11751aCDK6ampPD9467PD9467aChr8:(ZNF703 / FGFR1)ampPD11379PD11379aChr8:(ZNF703 / FGFR1)ampPD18188PD18188aChr8:(ZNF703 / FGFR1)ampPD9760PD9760aChr8:(ZNF703 / FGFR1)ampPD13608PD13608aChr8:(ZNF703 / FGFR1)ampPD22365PD22365aChr8:(ZNF703 / FGFR1)ampPD18257PD18257aChr8:(ZNF703 / FGFR1)ampPD8979PD8979aChr8:(ZNF703 / FGFR1)ampPD13425PD13425aChr8:(ZNF703 / FGFR1)ampPD4264PD4264aChr8:(ZNF703 / FGFR1)ampPD4965PD4965aChr8:(ZNF703 / FGFR1)ampPD9464PD9464aChr8:(ZNF703 / FGFR1)ampPD11368PD11368aChr8:(ZNF703 / FGFR1)ampPD6719PD6719aChr8:(ZNF703 / FGFR1)ampPD9599PD9599aChr8:(ZNF703 / FGFR1)ampPD13630PD13630aChr8:(ZNF703 / FGFR1)ampPD13165PD13165aChr8:(ZNF703 / FGFR1)ampPD9002PD9002aChr8:(ZNF703 / FGFR1)ampPD9759PD9759aChr8:(ZNF703 / FGFR1)ampPD9694PD9694aChr8:(ZNF703 / FGFR1)ampPD4978PD4978aChr8:(ZNF703 / FGFR1)ampPD9009PD9009aChr8:(ZNF703 / FGFR1)ampPD14453PD14453aChr8:(ZNF703 / FGFR1)ampPD11760PD11760aChr8:(ZNF703 / FGFR1)ampPD7240PD7240aChr8:(ZNF703 / FGFR1)ampPD13168PD13168aChr8:(ZNF703 / FGFR1)ampPD5951PD5951aChr8:(ZNF703 / FGFR1)ampPD7202PD7202aChr8:(ZNF703 / FGFR1)ampPD18189PD18189aChr8:(ZNF703 / FGFR1)ampPD11339PD11339aChr8:(ZNF703 / FGFR1)ampPD11394PD11394aChr8:(ZNF703 / FGFR1)ampPD7215PD7215aChr8:(ZNF703 / FGFR1)ampPD4315PD4315aChr8:(ZNF703 / FGFR1)ampPD11399PD11399aChr8:(ZNF703 / FGFR1)ampPD8980PD8980aChr8:(ZNF703 / FGFR1)ampPD5959PD5959aChr8:(ZNF703 / FGFR1)ampPD3904PD3904aChr8:(ZNF703 / FGFR1)ampPD8660PD8660a2Chr8:(ZNF703 / FGFR1)ampPD14457PD14457aChr8:(ZNF703 / FGFR1)ampPD4605PD4605aChr8:(ZNF703 / FGFR1)ampPD6048PD6048aChr8:(ZNF703 / FGFR1)ampPD9604PD9604aChr8:(ZNF703 / FGFR1)ampPD11340PD11340aChr8:(ZNF703 / FGFR1)ampPD4845PD4845aChr8:(ZNF703 / FGFR1)ampPD11741PD11741aChr8:(ZNF703 / FGFR1)ampPD18748PD18748aChr8:(ZNF703 / FGFR1)ampPD14461PD14461aChr8:(ZNF703 / FGFR1)ampPD9567PD9567aChr8:(ZNF703 / FGFR1)ampPD6044PD6044aChr8:(ZNF703 / FGFR1)ampPD14471PD14471aChr8:(ZNF703 / FGFR1)ampPD8981PD8981aChr8:(ZNF703 / FGFR1)ampPD6732PD6732bChr8:(ZNF703 / FGFR1)ampPD11369PD11369aChr8:(ZNF703 / FGFR1)ampPD9752PD9752aChr8:(ZNF703 / FGFR1)ampPD4976PD4976aChr8:(ZNF703 / FGFR1)ampPD9539PD9539aChr8:(ZNF703 / FGFR1)ampPD18045PD18045aChr8:(ZNF703 / FGFR1)ampPD18031PD18031aChr8:(ZNF703 / FGFR1)ampPD11374PD11374aChr8:(ZNF703 / FGFR1)ampPD18733PD18733aChr8:(ZNF703 / FGFR1)ampPD4255PD4255aChr8:(ZNF703 / FGFR1)ampPD24182PD24182aChr8:(ZNF703 / FGFR1)ampPD18047PD18047aChr8:(ZNF703 / FGFR1)ampPD7344PD7344aChr8:(ZNF703 / FGFR1)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 Table 7C Sample Gene Rearrangements PD8982aARID1B1|Tandem duplicationPD13299aARID1B2|Translocation|TranslocationPD7215aARID1B1|TranslocationPD13165aARID1B1|Tandem duplicationPD5932aARID1B1|DeletionPD9760aARID1B1|DeletionPD4956aARID1B1|Tandem duplicationPD4116aARID1B1|TranslocationPD4315aARID1B2|Translocation|DeletionPD24212aARID1B1|InversionPD7341aARID1B4|Inversion|Translocation|Deletion|InversionPD24303aARID1B1|TranslocationPD14437aARID1B4|Inversion|Deletion|Deletion|Tandem duplicationPD9592aARID1B1|Tandem duplicationPD5942aARID1B1|DeletionPD5948aARID1B1|Tandem duplicationPD5930aARID1B1|TranslocationPD4248aARID1B2|Tandem duplication|DeletionPD5956aARID1B1|Tandem duplicationPD23577aARID1B2|Translocation|TranslocationPD11396aARID1B2|Deletion|TranslocationPD11818aARID1B3|Tandem duplication|Deletion|InversionPD23567aARID1B1|TranslocationPD23566aARID1B1|Tandem duplicationPD24208aCDKN2A1|Tandem duplicationPD5925aCDKN2A1|DeletionPD7316aCDKN2A1|DeletionPD13602aCDKN2A1|DeletionPD24337aCDKN2A1|DeletionPD13752aCDKN2A2|Translocation|TranslocationPD4005aFBXW71 |TranslocationPD24201aFBXW71|Tandem duplicationPD7248aFBXW71|InversionPD9702aFBXW71|DeletionPD4844aFBXW72|Translocation|TranslocationPD4315aFBXW71|Tandem duplicationPD6404aFBXW71|DeletionPD7211aFBXW71|Tandem duplicationPD5948aFBXW71|DeletionPD10011aFBXW71|Tandem duplicationPD4255aFBXW71|Tandem duplicationPD11762aFBXW72|Deletion|InversionPD4845aFBXW71|Tandem duplicationPD23566aFBXW71|Tandem duplicationPD13425aMAP2K41|Tandem duplicationPD9597aMAP2K41 |TranslocationPD9572aMAP2K41|InversionPD7305aMAP2K42|Inversion|TranslocationPD14437aMAP2K41|DeletionPD22355aMAP2K42|Translocation|TranslocationPD14441aMAP2K42|Inversion|TranslocationPD11761aMAP2K41|DeletionPD14454aMAP2K41|DeletionPD11380aMAP2K41|DeletionPD6417aMAP2K41|TranslocationPD11385aMAP2K41|DeletionPD9754aMAP2K41|Tandem duplicationPD13626aMAP2K41|InversionPD22361aMAP3K11|Tandem duplicationPD13307aMAP3K11|TranslocationPD4956aMAP3K11|TranslocationPD22360aMAP3K11|TranslocationPD4847aMAP3K11|Tandem duplicationPD4836aMAP3K11|DeletionPD13602aMAP3K11|Tandem duplicationPD7201aMAP3K12|Deletion|Tandem duplicationPD4225aMAP3K13|Inversion|Inversion|DeletionPD8618aMAP3K11|DeletionPD11740aMAP3K11|DeletionPD6722aPTEN1|DeletionPD22357aPTEN1|InversionPD7426aPTEN2|Inversion|InversionPD7217aPTEN1|DeletionPD7248aPTEN1|Tandem duplicationPD9004aPTEN1|DeletionPD6733bPTEN2|Deletion|DeletionPD4116aPTEN1|DeletionPD9585aPTEN1|Tandem duplicationPD9702aPTEN2|Tandem duplication|Tandem duplicationPD8984aPTEN1|DeletionPD7321aPTEN1|Tandem duplicationPD24202aPTEN1|Tandem duplicationPD8611aPTEN2|Tandem duplication|Tandem duplicationPD9575aPTEN1|InversionPD6413aPTEN2|Inversion|TranslocationPD8964aPTEN1|DeletionPD6410aPTEN2|Inversion|InversionPD9696aPTEN1|DeletionPD11327aPTEN1|DeletionPD9752aPTEN1|InversionPD8621aPTEN1|Tandem duplicationPD24303aPTEN1|Tandem duplicationPD7211aPTEN1|Tandem duplicationPD11347aPTEN1|DeletionPD11757aPTEN1|DeletionPD5948aPTEN1|Tandem duplicationPD9595aPTEN1|DeletionPD7316aPTEN1|DeletionPD5934aPTEN1|Tandem duplicationPD24186aPTEN1|DeletionPD5960aPTEN1|DeletionPD6406aPTEN1|Tandem duplicationPD23563aPTEN1|DeletionPD9571aPTEN1|DeletionPD10010aPTEN1|DeletionPD11755aPTEN1|Tandem duplicationPD24306aPTEN1|Tandem duplicationPD9579aPTEN1|DeletionPD13622aPTEN1|DeletionPD24200aPTEN1|DeletionPD6731a2RB12|Inversion|InversionPD7426aRB11|DeletionPD6684aRB11|Tandem duplicationPD18769aRB11|DeletionPD6415aRB11|TranslocationPD4005aRB11|Tandem duplicationPD13296aRB11|Tandem duplicationPD22366aRB11|Tandem duplicationPD9585aRB11|DeletionPD9702aRB11|Tandem duplicationPD7321aRB11|DeletionPD11326aRB11|Tandem duplicationPD9064aRB11|Tandem duplicationPD3905aRB11|Tandem duplicationPD8621aRB11|Tandem duplicationPD23562aRB11|DeletionPD5928aRB12|Translocation|TranslocationPD5945aRB11|Tandem duplicationPD9592aRB11|DeletionPD5930aRB11 |TranslocationPD7250aRB11|Tandem duplicationPD23578aRB11|DeletionPD13428aRB11|DeletionPD24304aRB12|Inversion|InversionPD5944aRB11|DeletionPD23566aRB11|Tandem duplicationPD11344aTP531|TranslocationPD13771aTP531|DeletionPD4952aTP531|DeletionPD4116aTP531|DeletionPD24190aTP531|DeletionPD11340aTP531|DeletionPD13602aTP531|Tandem duplicationPD5961aTP531|TranslocationPD24218aTP531|DeletionPD6414aTP531|Tandem duplicationPD4845aTP531|Tandem duplicationPD8660a2MLLT41|Tandem duplicationPD11750aMLLT41|TranslocationPD4005aMLLT41|TranslocationPD11751aMLLT41|TranslocationPD9585aMLLT43|Translocation|Translocation|Tandem duplicationPD9702aMLLT41|Tandem duplicationPD9595aMLLT41|DeletionPD8997aMLLT41|DeletionPD23563aMLLT41|InversionPD11380aMLLT41|DeletionPD4264aMLLT41|InversionPD11752aMLLT41|Tandem duplicationPD8996aMLLT41|DeletionPD5956aMLLT41|DeletionPD24329aMLLT41 |TranslocationPD23577aMLLT41|Tandem duplication Table 7D Sample Tumour_name Gene Mutation_Type Effect PD11389PD11389aAKT1SubmissensePD9845PD9845aAKT1SubmissensePD8977PD8977aAKT1SubmissensePD4248PD4248aAKT1SubmissensePD14453PD14453aAKT1SubmissensePD6043PD6043aAKT1SubmissensePD9572PD9572aAKT1SubmissensePD14462PD14462aAKT1SubmissensePD8609PD8609aAKT1SubmissensePD22364PD22364aAKT1SubmissensePD11765PD11765aAKT1SubmissensePD13428PD13428aAKT1SubmissensePD17973PD17973aAKT1SubmissensePD24216PD24216aAKT1SubmissensePD24201PD24201aAKT1CopyNumberampPD8997PD8997aAKT1CopyNumberampPD9001PD9001aAKT1CopyNumberampPD9541PD9541aAKT2SubmissensePD13424PD13424aAKT2CopyNumberampPD14457PD14457aAKT2CopyNumberampPD24190PD24190aAKT2CopyNumberampPD8660PD8660a2AKT2CopyNumberampPD11365PD11365aAPCInsframeshiftPD9065PD9065aARID1ADelframeshiftPD14467PD14467aARID1ADelframeshiftPD9760PD9760aARID1AInsframeshiftPD9063PD9063aARID1ASubnonsensePD7322PD7322aARID1ASubnonsensePD11375PD11375aARID1ADelframeshiftPD4613PD4613aARID1ASubnonsensePD17981PD17981aARID1ADelframeshiftPD5937PD5937aARID1AInsframeshiftPD11402PD11402aARID1AInsframeshiftPD5937PD5937aARID1ADelframeshiftPD11399PD11399aARID1ADelinframePD7250PD7250aARID1ADelframeshiftPD11381PD11381aARID1AInsframeshiftPD11397PD11397aARID1ASubnonsensePD7206PD7206aARID1ASubnonsensePD14441PD14441aARID1ADelframeshiftPD23579PD23579aARID1BInsframeshiftPD9063PD9063aARID1BSubnonsensePD4252PD4252aARID1BSubnonsensePD4844PD4844aARID1BDelframeshiftPD8982PD8982aARID1BRearrangement1|Tandem duplicationPD13299PD13299aARID1BRearrangement2|Translocation| TranslocationPD7215PD7215aARID1BRearrangement1|TranslocationPD13165PD13165aARID1BRearrangement1|Tandem duplicationPD5932PD5932aARID1BRearrangement1|DeletionPD9760PD9760aARID1BRearrangement1|DeletionPD4956PD4956aARID1BRearrangement1|Tandem duplicationPD4116PD4116aARID1BRearrangement1|TranslocationPD4315PD4315aARID1BRearrangement2|Translocation| DeletionPD24212PD24212aARID1BRearrangement1|InversionPD7341PD7341aARID1BRearrangement4|Inversion| Translocation| Deletion|InversionPD24303PD24303aARID1BRearrangement1|TranslocationPD14437PD14437aARID1BRearrangement4|Inversion|Deletion| Deletion|Tandem duplicationPD9592PD9592aARID1BRearrangement1|Tandem duplicationPD5942PD5942aARID1BRearrangement1|DeletionPD5948PD5948aARID1BRearrangement1|Tandem duplicationPD5930PD5930aARID1BRearrangement1|TranslocationPD4248PD4248aARID1BRearrangement2|Tandem duplication| DeletionPD5956PD5956aARID1BRearrangement1|Tandem duplicationPD23577PD23577aARID1BRearrangement2|Translocation| TranslocationPD11396PD11396aARID1BRearrangement2|Deletion|TranslocationPD11818PD11818aARID1BRearrangement3|Tandem duplication| Deletion| InversionPD23567PD23567aARID1BRearrangement1|TranslocationPD23566PD23566aARID1BRearrangement1|Tandem duplicationPD10011PD10011aASXL1DelframeshiftPD5937PD5937aATMSubnonsensePD4198PD4198aATMSubmissensePD14457PD14457aATRSubnonsensePD23564PD23564aATRDelframeshiftPD5956PD5956aATRDelframeshiftPD18749PD18749aATRXSubnonsensePD11462PD11462aATRXSubess splicePD5937PD5937aAXIN1InsframeshiftPD6412PD6412aAXIN1SubmissensePD4958PD4958aBCORSubess splicePD4109PD4109aBCORSubnonsensePD24333PD24333aBRAFSubmissensePD11742PD11742aBRCA1InsframeshiftPD7215PD7215aBRCA1SubmissensePD9585PD9585aBRCA1SubnonsensePD7067PD7067aBRCA1SubnonsensePD23561PD23561aBRCA1InsframeshiftPD13604PD13604aBRCA2SubnonsensePD11372PD11372aBRCA2SubnonsensePD24191PD24191aBRCA2DelframeshiftPD23565PD23565aBRCA2SubnonsensePD13604PD13604aBRCA2SubnonsensePD6042PD6042aBRCA2SubnonsensePD24326PD24326aBRCA2SubnonsensePD9000PD9000aBRCA2DelframeshiftPD8978PD8978aBRCA2DelframeshiftPD8984PD8984aBRCA2InsframeshiftPD5960PD5960aBRCA2CopyNumberHDPD23579PD23579aBUB1BDelframeshiftPD4607PD4607aCASP8SubnonsensePD7209PD7209aCBFBSubstart-lostPD7210PD7210aCBFBSubess splicePD13310PD13310aCBFBSubnonsensePD18046PD18046aCBFBSubnonsensePD9761PD9761aCBFBSubess splicePD13762PD13762aCBFBSubess splicePD17973PD17973aCBFBSubess splicePD18047PD18047aCBFBInsess splicePD4982PD4982aCBFBSubess splicePD14458PD14458aCBFBSubess splicePD4972PD4972aCBFBInsframeshiftPD4976PD4976aCBFBInsframeshiftPD18269PD18269aCBFBSubnonsensePD7218PD7218aCBFBDelframeshiftPD18756PD18756aCBFBSubess splicePD6044PD6044aCBLBDelframeshiftPD11337PD11337aCCND1CopyNumberampPD11340PD11340aCCND1CopyNumberampPD11343PD11343aCCND1CopyNumberampPD11346PD11346aCCND1CopyNumberampPD11348PD11348aCCND1CopyNumberampPD11360PD11360aCCND1CopyNumberampPD11372PD11372aCCND1CopyNumberampPD11374PD11374aCCND1CopyNumberampPD11385PD11385aCCND1CopyNumberampPD11393PD11393aCCND1CopyNumberampPD11394PD11394aCCND1CopyNumberampPD11396PD11396aCCND1CopyNumberampPD11399PD11399aCCND1CopyNumberampPD11741PD11741aCCND1CopyNumberampPD11760PD11760aCCND1CopyNumberampPD11761PD11761aCCND1CopyNumberampPD13163PD13163aCCND1CopyNumberampPD13168PD13168aCCND1CopyNumberampPD13302PD13302aCCND1CopyNumberampPD13307PD13307aCCND1CopyNumberampPD13424PD13424aCCND1CopyNumberampPD13606PD13606aCCND1CopyNumberampPD13607PD13607aCCND1CopyNumberampPD13608PD13608aCCND1CopyNumberampPD13620PD13620aCCND1CopyNumberampPD13630PD13630aCCND1CopyNumberampPD13766PD13766aCCND1CopyNumberampPD13771PD13771aCCND1CopyNumberampPD14433PD14433aCCND1CopyNumberampPD14435PD14435aCCND1CopyNumberampPD14459PD14459aCCND1CopyNumberampPD14460PD14460aCCND1CopyNumberampPD14461PD14461aCCND1CopyNumberampPD14462PD14462aCCND1CopyNumberampPD14465PD14465aCCND1CopyNumberampPD14467PD14467aCCND1CopyNumberampPD14473PD14473aCCND1CopyNumberampPD17981PD17981aCCND1CopyNumberampPD18251PD18251aCCND1CopyNumberampPD18257PD18257aCCND1CopyNumberampPD18751PD18751aCCND1CopyNumberampPD22362PD22362aCCND1CopyNumberampPD23550PD23550aCCND1CopyNumberampPD24199PD24199aCCND1CopyNumberampPD24219PD24219aCCND1CopyNumberampPD24327PD24327aCCND1CopyNumberampPD24332PD24332aCCND1CopyNumberampPD4103PD4103aCCND1CopyNumberampPD4116PD4116aCCND1CopyNumberampPD4198PD4198aCCND1CopyNumberampPD4315PD4315aCCND1CopyNumberampPD4959PD4959aCCND1CopyNumberampPD4965PD4965aCCND1CopyNumberampPD4969PD4969aCCND1CopyNumberampPD4971PD4971aCCND1CopyNumberampPD4976PD4976aCCND1CopyNumberampPD5946PD5946aCCND1CopyNumberampPD5951PD5951aCCND1CopyNumberampPD5956PD5956aCCND1CopyNumberampPD5964PD5964aCCND1CopyNumberampPD6044PD6044aCCND1CopyNumberampPD6045PD6045aCCND1CopyNumberampPD6046PD6046aCCND1CopyNumberampPD6047PD6047aCCND1CopyNumberampPD6048PD6048aCCND1CopyNumberampPD7069PD7069aCCND1CopyNumberampPD7202PD7202aCCND1CopyNumberampPD7204PD7204aCCND1CopyNumberampPD7305PD7305aCCND1CopyNumberampPD7306PD7306aCCND1CopyNumberampPD7322PD7322aCCND1CopyNumberampPD7341PD7341aCCND1CopyNumberampPD8609PD8609aCCND1CopyNumberampPD8977PD8977aCCND1CopyNumberampPD8980PD8980aCCND1CopyNumberampPD8995PD8995aCCND1CopyNumberampPD8999PD8999aCCND1CopyNumberampPD9539PD9539aCCND1CopyNumberampPD9541PD9541aCCND1CopyNumberampPD9567PD9567aCCND1CopyNumberampPD9582PD9582aCCND1CopyNumberampPD9591PD9591...

Claims

1. A computer-implemented method of determining a prognosis of a tumour or determining the suitability of a treatment for a tumour, the method including: characterising a DNA sample obtained from said tumour, by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and determining the prognosis or suitability of the treatment from the interpreted profile.

2. A computer-implemented method of selecting a patient for a clinical trial of a cancer therapy, the method including: characterising a DNA sample obtained from a tumour in said patient, by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and determining whether or not the patient is suitable for the clinical trial on the basis of the profile constructed for that patient.

3. A computer-implemented method of classifying a plurality of patients undergoing treatment for cancer, or participating in a clinical trial, the method including allocating patients to groups based on a profile constructed from a DNA sample obtained from a tumour in each patient by a method comprising the steps of: characterising a DNA sample obtained from said tumour, by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e).

4. A computer-implemented method of classifying patients who have completed a clinical trial or course of treatment, the method including: characterising a DNA sample obtained from a tumour in each of said patient by performing three or more of the following steps a) to e): a) determining a catalogue of base substitution signatures which are present in the sample; b) determining a catalogue of rearrangement signatures which are present in the sample, using a rearrangement classification that classifies rearrangements: (i) between clustered and non-clustered, (ii) between deletions, inversions, translocations and tandem duplications, and (iii) by size of the deletions, inversions and tandem duplications; c) determining a catalogue of insertion / deletion signatures which are present in the sample d) determining the overall copy number profile in the sample e) identifying putative driver mutations present in the sample and based on said determinations and identifications, constructing an interpreted profile of the tumour, wherein the three or more steps a) to e) include at least steps a), b) and c); steps a), b) and d); steps a), b) and e); steps b), c) and d); steps b), d) and e); or steps b), c) and e); and correlating the interpreted profile obtained for each patient with the clinical outcome of the trial or treatment.

5. The method according to any one of the preceding claims, further including the steps of: f) identifying putative recurrently mutated non-coding sites, and using the identified putative recurrently mutated non-coding sites in constructing the interpreted profile, and optionally further including the step of: g) obtaining a biologically useful over-arching summary of the sample, and using the obtained summary in constructing the interpreted profile.

6. The method according to any one of the preceding claims, wherein the method comprises identifying whether the sample has a high or low likelihood of being homologous recombination (HR)-deficient by performing the steps of: determining the presence or absence of a plurality of base substitution signatures, rearrangement signatures and insertion / deletion (indel) signatures in the sample and copy number profiles for the sample; generating, from the presence or absence of said plurality of base substitution signatures, rearrangement signatures and indel signatures in the sample and the copy number profiles for the sample, a probabilistic score; and based on said probabilistic score, identifying whether said sample has a high or low likelihood of being homologous recombination (HR)-deficient.

7. The method according to any one of the preceding claims further including the steps of: h) identifying the presence of mis-match repair (MMR) deficiency in the sample by using the presence or absence of base substitution signatures and indel signatures, and using this identification in constructing the interpreted profile.

8. The method according to any one of the preceding claims further including the steps of: i) identifying mutational characteristics in the sample that are informative of pathophysiological processes that are targetable including signatures relating to the immunological responses or to other DNA damage response processes, and using the identified characteristics in constructing the interpreted profile.

9. The method according to any one of the preceding claims wherein the catalogue of base substitution signatures is obtained by: cataloguing the somatic mutations in said sample to produce a mutational catalogue for that sample; determining the contributions of known mutational signatures to said mutational catalogue by determining a scalar factor for each of a plurality of said known mutational signatures which together minimize a function representing the difference between the mutations in said catalogue and the mutations expected from a combination of said plurality of known mutational signatures scaled by said scalar factors; and if the scalar factor corresponding to any one of said mutational signatures exceeds a predetermined threshold, including said mutation signature in the catalogue of base substitution signatures for the sample.

10. The method according to any one of the preceding claims wherein the catalogue of rearrangement signatures is obtained by: cataloguing the somatic mutations in said sample to produce a rearrangement catalogue for that sample which classifies identified rearrangement mutations in the sample using said rearrangement classification; determining the contributions of known rearrangement signatures to said rearrangement catalogue by computing the cosine similarity between the rearrangement mutations in said catalogue and the known rearrangement signatures; and if the number or proportion of rearrangements in the rearrangement catalogue which are determined to be associated with one of said rearrangement signatures exceeds a predetermined threshold, including said rearrangement signature in the catalogue of rearrangement signatures for the sample.

11. The method according to any one of the preceding claims wherein the method includes all of the steps a) to e).

12. A computer program product containing non-transitory memory storing a computer program which, when run on a computer, performs the method of any one of the preceding claims.

13. A computer having a processor, wherein the processor is configured to perform the method of any one or more of claims 1 to 11.