Submissions for variant NM_001035.3(RYR2):c.14029C>T (p.Leu4677=)

gnomAD frequency: 0.00446  dbSNP: rs112864477

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036688	SCV000060343	benign	not specified	2012-03-14	criteria provided, single submitter	clinical testing	Leu4677Leu in exon 97 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and has been identifie d in 1.7% (52/3126) of African American chromosomes from a broad population by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs112 864477).
Eurofins Ntd Llc (ga)	RCV000036688	SCV000111248	benign	not specified	2013-07-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000036688	SCV000171438	benign	not specified	2013-04-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001096508	SCV000285702	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-31	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000030412	SCV000900162	benign	Cardiomyopathy	2016-04-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001096507	SCV001252725	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	RCV001096508	SCV001252726	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.
Color Diagnostics, LLC DBA Color Health	RCV000030412	SCV001356050	benign	Cardiomyopathy	2018-03-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030412	SCV000053081	benign	Cardiomyopathy	2014-05-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529761	SCV001743780	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036688	SCV001924707	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529761	SCV001972522	likely benign	not provided		no assertion criteria provided	clinical testing