Submissions for variant NM_001134363.3(RBM20):c.2318A>G (p.Lys773Arg)

gnomAD frequency: 0.00324  dbSNP: rs181769913

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000180559	SCV000233023	benign	not specified	2015-05-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000180559	SCV000236314	benign	not specified	2014-06-26	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000180559	SCV000269745	benign	not specified	2015-05-20	criteria provided, single submitter	clinical testing	p.Lys773Arg in exon 9 of RBM20: This variant is not expected to have clinical si gnificance because it has been identified in 0.9% (20/2126) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org) an d in 8.4% (19/226) of Gambian chromosomes by the 1000 Genomes Project (dbSNP rs1 81769913).
Ambry Genetics	RCV000244273	SCV000319705	benign	Cardiovascular phenotype	2019-01-08	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV000466145	SCV000562789	benign	Dilated cardiomyopathy 1DD	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000466145	SCV001265837	uncertain significance	Dilated cardiomyopathy 1DD	2018-01-15	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170926	SCV001333574	benign	Cardiomyopathy	2018-02-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000180559	SCV001362407	benign	not specified	2019-12-16	criteria provided, single submitter	clinical testing	Variant summary: RBM20 c.2318A>G (p.Lys773Arg) 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 0.00075 in 156524 control chromosomes, predominantly at a frequency of 0.01 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 400 fold of the estimated maximal expected allele frequency for a pathogenic variant in RBM20 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (3x benign, 1x likely benign). Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001529847	SCV004127484	benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	RBM20: BP4, BS1, BS2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529847	SCV001744030	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000180559	SCV001922638	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529847	SCV001955352	likely benign	not provided		no assertion criteria provided	clinical testing