ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.2452G>T (p.Ala818Ser) (rs200271618)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036965 SCV000060621 uncertain significance not specified 2015-02-20 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000036965 SCV000236315 likely benign not specified 2015-07-09 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 RCV001083431 SCV000552931 likely benign Dilated cardiomyopathy 1DD 2020-11-21 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845312 SCV000987354 uncertain significance not provided criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000845312 SCV001148093 likely benign not provided 2019-04-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001083431 SCV001265838 uncertain significance 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170927 SCV001333575 benign Cardiomyopathy 2018-07-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036965 SCV001426805 likely benign not specified 2020-07-20 criteria provided, single submitter clinical testing Variant summary: RBM20 c.2452G>T (p.Ala818Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00032 in 123062 control chromosomes, predominantly at a frequency of 0.00056 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 11.95 fold of the estimated maximal expected allele frequency for a pathogenic variant in RBM20 causing Dilated Cardiomyopathy phenotype (4.7e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.2452G>T in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign/likely benign n=4, VUS n=2). Based on the evidence outlined above, the variant was classified as likely benign.

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