Search our database of validated splicing mutations

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GRCh37
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A peer-reviewed manuscript describing this resource is available through F1000Research
Shirley BC, Mucaki EJ, Rogan PK. Pan-cancer repository of validated natural and cryptic mRNA splicing mutations F1000Research 2019, 7:1908 (https://doi.org/10.12688/f1000research.17204.2)

Information Theory is proven to accurately predict the impact a mutation has on mRNA splicing, and has been used to interpret coding and non-coding mutations that alter mRNA splicing in both common and rare diseases (Caminsky et al., 2014; Burke et al., 2018; Dos Santos et al., 2018; Yang et al., 2017; Caminsky et al., 2016; Mucaki et al., 2016; Peterlongo et al., 2014; Mucaki et al., 2013; Mucaki et al., 2011; Rogan et al., 2003; Rogan et al., 1998; Rogan and Schneider, 1995). Mucaki et al. (2016) describes an information-theory based framework for the interpretation and prioritization of non-coding variants of uncertain significance, which has been applied in multiple studies involving novel variants in cancer patients (Burke et al., 2018; Dos Santos et al., 2018; Caminsky et al., 2016; Mucaki et al., 2016). The Information-Theory based software used in these studies is available in the bioinformatic suite MutationForecaster (www.mutationforecaster.com). This resource includes the Shannon Pipeline (which can quickly analyze millions of variants for their impact on mRNA splicing; Shirley et al., 2013) and Veridical (which validates Shannon Pipeline output by analyzing RNAseq BAM files for mutated splicing in patients with the variant of interest; Viner et al., 2014 and Dorman et al., 2014).

We examined variants obtained through The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) from thousands of patients. Using the Shannon Pipeline and Veridical, we analyzed over 209 million variants (>168 million TCGA variants in 33 cancer types, >41 million ICGC variants in 7 cancer types) and validated 341,486 variants for their direct impact on mRNA splicing. The user can query the resource for a mutation (or a range of coordinates containing mutations). This resource provides the user with the expected change in splice site strength caused by the variant of interest, and the observed mutant splicing event (i.e. sequencing reads which indicate cryptic site use). For some mutations, an image of the RNAseq data for the region of interest is provided. Expression levels of the gene containing the mutation can also be toggled for different tissues.

The following is a breakdown of all unique splicing mutations found in each TCGA tumor type (variants unique in a per-tissue basis; novel or < 1% of population [dbSNP150] are counted):

Tumor TypeTumor Description# Unique Variants
TCGA-ACCAdrenocortical Carcinoma1717
TCGA-LAMLAcute Myeloid Leukemia19503
TCGA-BRCABladder Urothelial Carcinoma24181
TCGA-BLCABreast Invasive Carcinoma9865
TCGA-CESCCervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma25822
TCGA-CHOLCholangiocarcinoma9817
TCGA-COADColon Adenocarcinoma7512
TCGA-DLBCLymphoid Neoplasm Diffuse Large B-cell Lymphoma6036
TCGA-ESCAEsophageal Carcinoma19361
TCGA-GBMGlioblastoma Multiforme935
TCGA-HNSCHead and Neck Squamous Cell Carcinoma2840
TCGA-KICHKidney Chromophobe26519
TCGA-KIRCKidney Renal Clear Cell Carcinoma6711
TCGA-KIRPKidney Renal Papillary Cell Carcinoma4892
TCGA-LGGBrain Lower Grade Glioma1346
TCGA-LIHCLiver Hepatocellular Carcinoma12461
TCGA-LUADLung Adenocarcinoma18262
TCGA-LUSCLung Squamous Cell Carcinoma2628
TCGA-MESOMesothelioma303
TCGA-OVOvarian Serous Cystadenocarcinoma88136
TCGA-PAADPancreatic Adenocarcinoma1585
TCGA-PCPGPheochromocytoma and Paraganglioma90
TCGA-PRADProstate Adenocarcinoma944
TCGA-READRectum Adenocarcinoma3083
TCGA-SARCSarcoma20024
TCGA-SKCMSkin Cutaneous Melanoma12515
TCGA-STADStomach Adenocarcinoma20245
TCGA-TGCTTesticular Germ Cell Tumors467
TCGA-THCAThyroid carcinoma56962
TCGA-THYMThymoma16599
TCGA-UCECUterine Corpus Endometrial Carcinoma28524
TCGA-UCSUterine Carcinosarcoma10716
TCGA-UVMUveal Melanoma2498
ICGC-CLLEChronic Lymphocytic Leukemia2041
ICGC-ESADEsophageal Adenocarcinoma61
ICGC-LIRILiver Cancer2255
ICGC-MALYMalignant Lymphoma2652
ICGC-OVOvarian Cancer2818
ICGC-PACAPancreatic Cancer Endocrine Neoplasms3182
ICGC-RECARenal Cell Cancer4255