Submissions for variant NM_001035.3(RYR2):c.8209-3A>G

gnomAD frequency: 0.00047  dbSNP: rs376788358

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036795	SCV000060450	likely benign	not specified	2019-09-24	criteria provided, single submitter	clinical testing	The c.8209-3G>A variant in RYR2 is classified as likely benign because it has been identified in 0.15% (34/21760) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is located in the 3' splice region. Although a subset of computational tools predict a possible splicing impact, this information is not predictive enough to support pathogenicity in the absence of additional data. ACMG/AMP Criteria applied: BA1, PP3.
GeneDx	RCV001719734	SCV000235153	uncertain significance	not provided	2021-10-21	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported in ClinVar (ClinVar Variant ID# 43829; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 32746448)
Ambry Genetics	RCV000621356	SCV000736332	likely benign	Cardiovascular phenotype	2019-04-03	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513441	SCV001008090	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001175859	SCV001339638	likely benign	Cardiomyopathy	2019-09-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000036795	SCV003934697	benign	not specified	2023-05-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534781	SCV004737787	likely benign	RYR2-related disorder	2022-07-08	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).
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678751	SCV000804927	uncertain significance	Dilated cardiomyopathy with left ventricular noncompaction	2015-10-01	no assertion criteria provided	clinical testing