Submissions for variant NM_001035.3(RYR2):c.10254C>T (p.Asn3418=)

gnomAD frequency: 0.00264  dbSNP: rs138073811

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030408	SCV000053077	likely benign	Cardiomyopathy	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036647	SCV000060302	benign	not specified	2015-03-24	criteria provided, single submitter	clinical testing	p.Asn3418Asn in exon 71 of RYR2: This variant is not expected to have clinical s ignificance because it has been identified in 0.9% (104/11788) of South Asian ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs138073811).
Eurofins Ntd Llc (ga)	RCV000036647	SCV000232395	benign	not specified	2015-01-17	criteria provided, single submitter	clinical testing
Invitae	RCV001097851	SCV000285685	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242203	SCV000318760	likely benign	Cardiovascular phenotype	2016-05-31	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	RCV000030408	SCV000900157	benign	Cardiomyopathy	2017-01-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000030408	SCV000902731	likely benign	Cardiomyopathy	2018-03-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001097850	SCV001254169	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	RCV001097851	SCV001254170	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.
GeneDx	RCV001529668	SCV001881844	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001529668	SCV002544387	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001529668	SCV003799455	benign	not provided	2023-10-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532426	SCV004748107	benign	RYR2-related disorder	2019-04-08	criteria provided, single submitter	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).
All of Us Research Program, National Institutes of Health	RCV003996133	SCV004817807	likely benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529668	SCV001743507	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036647	SCV001923302	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000036647	SCV001927251	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036647	SCV001957787	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529668	SCV001964395	likely benign	not provided		no assertion criteria provided	clinical testing