ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.6320C>T (p.Thr2107Met) (rs370331492)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154820 SCV000204501 uncertain significance not specified 2013-07-18 criteria provided, single submitter clinical testing The Thr2107Met variant in RYR2 has not been reported in individuals with cardiom yopathy, but has been identified in 1/8286 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computationa l analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen 2, and SIFT) suggest that this variant may impact the protein, though this infor mation is not predictive enough to determine pathogenicity. Additional informati on is needed to fully assess the variant's clinical significance.
Invitae RCV000462358 SCV000541676 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2016-08-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 2107 of the RYR2 protein (p.Thr2107Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs370331492, ExAC 0.01%) but has not been reported in the literature in individuals with a RYR2-related disease. This variant occurs within one of the three regions of the RYR2 gene (N-terminal domain, central domain, or channel region) where other pathogenic variants have been reported to cluster (PMID: 19926015). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765090 SCV000896299 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 2; Catecholaminergic polymorphic ventricular tachycardia type 1 2018-10-31 criteria provided, single submitter clinical testing
Color RCV001179780 SCV001344553 uncertain significance Cardiomyopathy 2020-04-07 criteria provided, single submitter clinical testing

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