Submissions for variant NM_001035.3(RYR2):c.5619A>G (p.Ala1873=)

gnomAD frequency: 0.00046  dbSNP: rs373282364

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036769	SCV000060424	likely benign	not specified	2015-08-25	criteria provided, single submitter	clinical testing	p.Ala1873Ala in exon 37 of RYR2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 37/65998 European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org /; dbSNP rs373282364).
Ambry Genetics	RCV000245051	SCV000319041	likely benign	Cardiovascular phenotype	2016-07-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000309384	SCV000356319	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001093879	SCV000356320	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV001093879	SCV000554570	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777598	SCV000913463	likely benign	Cardiomyopathy	2018-03-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036769	SCV001362248	benign	not specified	2019-09-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001528654	SCV001870806	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528654	SCV001740756	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036769	SCV001923638	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528654	SCV001931827	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528654	SCV001958580	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528654	SCV001975971	likely benign	not provided		no assertion criteria provided	clinical testing