Submissions for variant NM_001035.3(RYR2):c.14481C>T (p.Ile4827=)

dbSNP: rs114303476

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036700	SCV000060355	benign	not specified	2012-02-08	criteria provided, single submitter	clinical testing	Classified as bening based on high frequency (0.03; 101/3186 AA chromosomes, NHL BI ESP)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001093844	SCV000285704	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2025-02-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000249207	SCV000318475	benign	Cardiovascular phenotype	2015-09-18	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	RCV000329225	SCV000356491	likely benign	Arrhythmogenic right ventricular dysplasia 2	2018-10-17	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001093844	SCV000356492	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2018-10-17	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768793	SCV000900165	benign	Cardiomyopathy	2016-04-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000768793	SCV000913465	benign	Cardiomyopathy	2018-03-15	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000036700	SCV001433076	benign	not specified	2020-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001711109	SCV001472941	benign	not provided	2023-09-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001711109	SCV001944387	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996260	SCV004820531	benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001711109	SCV005257472	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004534776	SCV004731459	benign	RYR2-related disorder	2019-09-18	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).