Submissions for variant NM_001035.3(RYR2):c.13137C>A (p.Ile4379=)

gnomAD frequency: 0.00021  dbSNP: rs369917806

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036675	SCV000060330	likely benign	not specified	2012-08-20	criteria provided, single submitter	clinical testing	Ile4379Ile in exon 90 of RYR2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 2/6674 European Ame rican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Ile4379Ile in exon 90 of RYR2 (allele frequ ency = 2/6674) **
GeneDx	RCV001529567	SCV000514457	likely benign	not provided	2020-10-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001101823	SCV000637505	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2025-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617184	SCV000736997	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: 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.
Color Diagnostics, LLC DBA Color Health	RCV000777845	SCV000913846	likely benign	Cardiomyopathy	2018-09-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001101823	SCV001258464	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2018-01-13	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	RCV001101824	SCV001258465	uncertain significance	Arrhythmogenic right ventricular dysplasia 2	2018-01-13	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.
All of Us Research Program, National Institutes of Health	RCV003996249	SCV004821063	likely benign	Catecholaminergic polymorphic ventricular tachycardia	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529567	SCV001743213	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529567	SCV001959244	likely benign	not provided		no assertion criteria provided	clinical testing