Submissions for variant NM_001035.3(RYR2):c.10035G>A (p.Arg3345=)

gnomAD frequency: 0.00004  dbSNP: rs754976419

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000253028	SCV000320128	likely benign	Cardiovascular phenotype	2015-09-04	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.
GeneDx	RCV000427858	SCV000514453	benign	not specified	2015-11-09	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001096093	SCV000760709	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2023-12-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001096092	SCV001252281	uncertain significance	Arrhythmogenic right ventricular dysplasia 2	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.
Illumina Laboratory Services, Illumina	RCV001096093	SCV001252282	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia 1	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.
Color Diagnostics, LLC DBA Color Health	RCV001179774	SCV001344546	benign	Cardiomyopathy	2018-11-27	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995719	SCV004815166	benign	Catecholaminergic polymorphic ventricular tachycardia	2023-12-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542953	SCV004763132	likely benign	RYR2-related disorder	2023-10-17	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).