Submissions for variant NM_001035.3(RYR2):c.1491C>T (p.Leu497=)

gnomAD frequency: 0.00007  dbSNP: rs774279425

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000601797	SCV000715785	likely benign	not specified	2017-02-07	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.
Color Diagnostics, LLC DBA Color Health	RCV000772675	SCV000905934	likely benign	Cardiomyopathy	2018-09-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002529422	SCV001008863	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-11-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001311689	SCV001501966	likely benign	not provided	2021-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002395555	SCV002700064	likely benign	Cardiovascular phenotype	2019-01-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
All of Us Research Program, National Institutes of Health	RCV004002498	SCV004846095	likely benign	Catecholaminergic polymorphic ventricular tachycardia	2024-01-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004740365	SCV005344835	likely benign	RYR2-related disorder	2024-07-08	no assertion criteria provided	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).