Submissions for variant NM_001035.3(RYR2):c.7365C>T (p.Asp2455=)

gnomAD frequency: 0.00413  dbSNP: rs72549416

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036789	SCV000060444	benign	not specified	2012-03-23	criteria provided, single submitter	clinical testing	Asp2455Asp in exon 49 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 0.6% (43/6656) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs72549416)
Eurofins Ntd Llc (ga)	RCV000036789	SCV000111255	benign	not specified	2013-03-12	criteria provided, single submitter	clinical testing
Invitae	RCV001093775	SCV000285746	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252487	SCV000318616	likely benign	Cardiovascular phenotype	2016-04-19	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.
Illumina Laboratory Services, Illumina	RCV000332748	SCV000356345	likely benign	Arrhythmogenic right ventricular dysplasia 2	2018-01-12	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001093775	SCV000356346	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2018-01-12	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	RCV000030427	SCV000901219	benign	Cardiomyopathy	2016-07-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000030427	SCV000902766	benign	Cardiomyopathy	2018-03-14	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000036789	SCV001433075	benign	not specified	2020-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001530135	SCV001845766	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001530135	SCV002048205	benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001530135	SCV002497005	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV004541031	SCV004786581	likely benign	RYR2-related disorder	2019-04-12	criteria provided, single submitter	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).
All of Us Research Program, National Institutes of Health	RCV003996143	SCV004822102	benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030427	SCV000053096	benign	Cardiomyopathy	2014-03-20	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001530135	SCV001744829	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036789	SCV001917972	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000036789	SCV001933021	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036789	SCV001952470	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001530135	SCV001965330	likely benign	not provided		no assertion criteria provided	clinical testing