Submissions for variant NM_001035.3(RYR2):c.2760G>A (p.Glu920=)

gnomAD frequency: 0.00205  dbSNP: rs186181155

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036721	SCV000060376	likely benign	not specified	2017-05-05	criteria provided, single submitter	clinical testing	p.Glu920Glu in exon 24 of RYR2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.3% (299/99440) o f European chromosomes, including 2 homozygotes, by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs186181155).
Eurofins Ntd Llc (ga)	RCV000724532	SCV000228123	uncertain significance	not provided	2015-03-02	criteria provided, single submitter	clinical testing
Invitae	RCV001093756	SCV000285716	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001093756	SCV000356253	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.
Illumina Laboratory Services, Illumina	RCV000368575	SCV000356254	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.
Ambry Genetics	RCV000618697	SCV000735203	likely benign	Cardiovascular phenotype	2015-09-18	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	RCV000769780	SCV000901205	benign	Cardiomyopathy	2017-09-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769780	SCV000910854	benign	Cardiomyopathy	2018-03-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036721	SCV001774654	benign	not specified	2021-07-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000724532	SCV001897889	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000724532	SCV002048993	benign	not provided	2022-10-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000724532	SCV004042471	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BP7, BS1
All of Us Research Program, National Institutes of Health	RCV003996268	SCV004815325	benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000724532	SCV001740894	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036721	SCV001924183	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000724532	SCV001928947	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036721	SCV001953328	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724532	SCV001964289	likely benign	not provided		no assertion criteria provided	clinical testing