Submissions for variant NM_001035.3(RYR2):c.10941T>G (p.Pro3647=)

gnomAD frequency: 0.00051  dbSNP: rs370332882

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151772	SCV000200190	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	Pro3647Pro in exon 78 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.1% (4/6562) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS). Pro3647Pro in exon 78 of RYR2 (al lele frequency = 0.1%, 4/6562) **
Labcorp Genetics (formerly Invitae), Labcorp	RCV001096209	SCV000285689	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2025-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621644	SCV000735863	likely benign	Cardiovascular phenotype	2017-05-15	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769804	SCV000901230	likely benign	Cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769804	SCV000903378	benign	Cardiomyopathy	2018-06-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000229147	SCV001147776	likely benign	not provided	2021-07-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001096208	SCV001252405	uncertain significance	Arrhythmogenic right ventricular dysplasia 2	2017-04-27	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001096209	SCV001252406	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2017-04-27	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000229147	SCV001474288	likely benign	not provided	2020-02-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000229147	SCV001916402	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000151772	SCV002500686	benign	not specified	2022-03-28	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003998227	SCV004816030	benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000229147	SCV001740974	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000151772	SCV001920362	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000229147	SCV001932711	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000151772	SCV001953953	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000229147	SCV001972695	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544362	SCV004773634	likely benign	RYR2-related disorder	2023-04-14	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).