Submissions for variant NM_001035.3(RYR2):c.7542G>A (p.Leu2514=)

gnomAD frequency: 0.00011  dbSNP: rs371088367

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182635	SCV000235008	benign	not specified	2014-07-02	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.
Ambry Genetics	RCV000252731	SCV000320557	likely benign	Cardiovascular phenotype	2015-12-01	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.
Illumina Laboratory Services, Illumina	RCV000343987	SCV000356351	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.
Illumina Laboratory Services, Illumina	RCV001093830	SCV000356352	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001093830	SCV000554594	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-12-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000777732	SCV000913689	likely benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003884379	SCV004699846	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BS1
All of Us Research Program, National Institutes of Health	RCV003996733	SCV004822551	likely benign	Catecholaminergic polymorphic ventricular tachycardia	2024-01-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537529	SCV004741634	likely benign	RYR2-related disorder	2024-08-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).