Submissions for variant NM_001134363.3(RBM20):c.1986G>A (p.Pro662=)

gnomAD frequency: 0.00233  dbSNP: rs537723089

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000156392	SCV000171319	benign	not specified	2013-03-18	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	RCV000156392	SCV000206110	benign	not specified	2015-07-22	criteria provided, single submitter	clinical testing	p.Pro662Pro in exon 9 of RBM20: This variant is not expected to have clinical si gnificance because it has been identified in 2.9% (22/770) of Finnish chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org.; db SNP rs537723089).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232829	SCV000286188	benign	Dilated cardiomyopathy 1DD	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000253168	SCV000318837	benign	Cardiovascular phenotype	2016-08-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Illumina Laboratory Services, Illumina	RCV000232829	SCV000360359	uncertain significance	Dilated cardiomyopathy 1DD	2018-01-13	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	RCV000769267	SCV000900643	likely benign	Cardiomyopathy	2016-07-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000156392	SCV001554565	benign	not specified	2021-03-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000232829	SCV004563149	benign	Dilated cardiomyopathy 1DD	2023-11-29	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000232829	SCV000732919	likely benign	Dilated cardiomyopathy 1DD		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000156392	SCV001925372	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000857911	SCV001931359	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000857911	SCV001957110	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000156392	SCV001975656	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935204	SCV004752620	benign	RBM20-related disorder	2019-11-19	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).