Submissions for variant NM_001035.3(RYR2):c.2574G>A (p.Thr858=)

gnomAD frequency: 0.00025  dbSNP: rs367992907

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182624	SCV000234990	benign	not specified	2014-09-18	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.
Illumina Laboratory Services, Illumina	RCV000404420	SCV000356249	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	RCV001093754	SCV000356250	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.
Invitae	RCV001093754	SCV000554572	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619882	SCV000735527	likely benign	Cardiovascular phenotype	2016-10-20	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769778	SCV000901203	uncertain significance	Cardiomyopathy	2016-05-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769778	SCV000904413	likely benign	Cardiomyopathy	2018-07-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001172025	SCV001334954	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BP7
Clinical Genetics, Academic Medical Center	RCV000182624	SCV001919315	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000182624	SCV001959043	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001172025	SCV001964624	likely benign	not provided		no assertion criteria provided	clinical testing