Submissions for variant NM_001134363.3(RBM20):c.2213C>T (p.Pro738Leu)

dbSNP: rs397516601

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036962	SCV000060618	likely benign	not specified	2014-09-29	criteria provided, single submitter	clinical testing	Phe738Leu in exon 9 of RBM20: This variant is not expected to have clinical sign ificance due to a lack of evolutionary conservation of the affected amino acid. Of note, >25 mammals, including 6 primates, have a leucine (Leu) at this positio n despite high nearby amino acid conservation, suggesting that this change is to lerated.
GeneDx	RCV001703878	SCV000236312	likely benign	not provided	2021-01-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000863923	SCV000360363	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.
Invitae	RCV000863923	SCV001004653	likely benign	Dilated cardiomyopathy 1DD	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426560	SCV002728317	likely benign	Cardiovascular phenotype	2020-03-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
PreventionGenetics, part of Exact Sciences	RCV003944901	SCV004775912	likely benign	RBM20-related condition	2022-02-07	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000036962	SCV001924061	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001703878	SCV001968321	likely benign	not provided		no assertion criteria provided	clinical testing