Submissions for variant NM_001035.3(RYR2):c.7233C>T (p.Ala2411=)

gnomAD frequency: 0.00046  dbSNP: rs367994477

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000242406	SCV000319922	likely benign	Cardiovascular phenotype	2015-07-17	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.
Invitae	RCV002518714	SCV000637603	benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-04	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000599644	SCV000710925	likely benign	not specified	2017-04-20	criteria provided, single submitter	clinical testing	p.Ala2411Ala in Exon 48 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 0.1% (21/23994) o f African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad. broadinstitute.org/; dbSNP rs367994477)
GeneDx	RCV000599644	SCV000729811	likely benign	not specified	2017-10-18	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.
Color Diagnostics, LLC DBA Color Health	RCV000777854	SCV000913856	benign	Cardiomyopathy	2018-10-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003417865	SCV004126214	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	RYR2: BP4, BP7, BS1
PreventionGenetics, part of Exact Sciences	RCV003909887	SCV004721081	likely benign	RYR2-related condition	2019-08-09	criteria provided, single submitter	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).