Submissions for variant NM_001035.3(RYR2):c.8448C>T (p.Asp2816=)

gnomAD frequency: 0.00659  dbSNP: rs144876996

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036799	SCV000060454	benign	not specified	2012-04-17	criteria provided, single submitter	clinical testing	Asp2816Asp in Exon 57 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.8% (54/6602) of Euro pean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs144876996).
Eurofins Ntd Llc (ga)	RCV000036799	SCV000111257	benign	not specified	2013-09-04	criteria provided, single submitter	clinical testing
Invitae	RCV001093776	SCV000285753	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000036799	SCV000306077	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000253351	SCV000318605	benign	Cardiovascular phenotype	2015-08-07	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	RCV000296842	SCV000356359	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001093776	SCV000356360	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768775	SCV000900145	benign	Cardiomyopathy	2015-11-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000768775	SCV000910637	benign	Cardiomyopathy	2018-03-15	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528825	SCV001159173	benign	not provided	2023-11-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001528825	SCV001939920	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996304	SCV004823409	benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528825	SCV001741231	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036799	SCV001924231	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036799	SCV001951233	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000036799	SCV001969251	benign	not specified		no assertion criteria provided	clinical testing