Submissions for variant NM_001134363.3(RBM20):c.2303C>T (p.Ser768Leu)

dbSNP: rs1417635

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036963	SCV000060619	benign	not specified	2012-07-17	criteria provided, single submitter	clinical testing	p.Trp768Leu in Exon 09 of RBM20: This variant is not expected to have clinical s ignificance because it has been identified in 2.6% (18/702) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs1417635).
GeneDx	RCV000036963	SCV000171322	benign	not specified	2014-05-12	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.
Ambry Genetics	RCV000247863	SCV000319866	benign	Cardiovascular phenotype	2015-09-17	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	RCV000464527	SCV000562786	benign	Dilated cardiomyopathy 1DD	2024-01-31	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769272	SCV000900648	benign	Cardiomyopathy	2016-06-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000464527	SCV001265836	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036963	SCV001362405	benign	not specified	2023-10-30	criteria provided, single submitter	clinical testing	Variant summary: RBM20 c.2303C>T (p.Ser768Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 156550 control chromosomes. The observed variant frequency is approximately 46 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 benign. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000464527	SCV003799280	benign	Dilated cardiomyopathy 1DD	2022-05-04	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036963	SCV001919764	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000036963	SCV001965367	benign	not specified		no assertion criteria provided	clinical testing