Submissions for variant NM_001035.3(RYR2):c.3153C>T (p.Arg1051=)

gnomAD frequency: 0.00013  dbSNP: rs397516524

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036725	SCV000060380	likely benign	not specified	2012-07-27	criteria provided, single submitter	clinical testing	Arg1051Arg in exon 27 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. Arg1051Arg in exon 27 of RYR2 (allele frequ ency = n/a)
Ambry Genetics	RCV000251649	SCV000319635	likely benign	Cardiovascular phenotype	2020-03-20	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.
GeneDx	RCV000036725	SCV000514436	likely benign	not specified	2016-02-08	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001097097	SCV000541683	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2025-01-19	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769782	SCV000901207	uncertain significance	Cardiomyopathy	2016-08-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769782	SCV000904649	likely benign	Cardiomyopathy	2018-10-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001097096	SCV001253348	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	RCV001097097	SCV001253349	uncertain significance	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, 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.