ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.1144G>A (p.Val382Met) (rs370057029)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182675 SCV000235054 uncertain significance not provided 2017-12-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR2 gene. The V382M variant has been reported in at least one heterozygous individual from a cohort of patients referred for clinical whole exome sequencing (Landstrom et al., 2017). The V382M variant is observed in 12/123682 (0.01%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The V382M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202980 SCV000257747 uncertain significance Catecholaminergic polymorphic ventricular tachycardia type 1 2015-06-17 criteria provided, single submitter clinical testing
Invitae RCV000699318 SCV000828023 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2020-01-09 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 382 of the RYR2 protein (p.Val382Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs370057029, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in the literature in an individual referred for genetic testing (PMID: 28404607). ClinVar contains an entry for this variant (Variation ID: 201209). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000777719 SCV000913663 uncertain significance Cardiomyopathy 2020-03-11 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001256935 SCV001433456 uncertain significance Arrhythmogenic right ventricular dysplasia, familial 1 2019-10-28 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.