ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.3373G>A (p.Glu1125Lys) (rs116908219)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036984 SCV000060640 benign not specified 2017-08-10 criteria provided, single submitter clinical testing p.Glu1125Lys in exon 12 of RBM20: This variant is classified as benign because i t has been identified in 1.8% (157/8538) of Ashkenazi Jewish chromosomes, includ ing 4 homozygotes by the Genome Aggregation Database (gnomAD, http://gmomad.broa dinstitute.org; dbSNP rs116908219).
GeneDx RCV000036984 SCV000236322 benign not specified 2018-01-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000226115 SCV000286203 benign Dilated cardiomyopathy 1DD 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000252174 SCV000318433 benign Cardiovascular phenotype 2018-06-25 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000036984 SCV000740658 likely benign not specified 2016-05-18 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770284 SCV000901716 likely benign Cardiomyopathy 2017-08-18 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852634 SCV000995339 benign Arrhythmogenic right ventricular cardiomyopathy; Long QT syndrome 2019-03-18 criteria provided, single submitter clinical testing
Mendelics RCV000226115 SCV001138172 likely benign Dilated cardiomyopathy 1DD 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000857871 SCV001148099 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000226115 SCV001262292 likely benign Dilated cardiomyopathy 1DD 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036984 SCV001339224 benign not specified 2020-03-30 criteria provided, single submitter clinical testing Variant summary: RBM20 c.3373G>A (p.Glu1125Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0036 in 156520 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 145-fold the estimated maximal expected allele frequency for a pathogenic variant in RBM20 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. c.3373G>A has been reported in the literature in individuals affected with Cardiomyopathy without strong evidence for causality (examples- Lopes_2013, Pugh_2014, Bottillo_2016, Jaaskelainen_2019). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. They have cited the variant as benign (n=4), likely benign (n=4) and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000226115 SCV000732928 likely benign Dilated cardiomyopathy 1DD no assertion criteria provided clinical testing

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