ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8342C>G (p.Thr2781Ser)

dbSNP: rs369963696
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151768 SCV000200181 uncertain significance not specified 2013-12-26 criteria provided, single submitter clinical testing The Thr2781Ser variant in RYR2 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Computational analyses (amino acid biochemical properties, conservation, SIFT, PolyPhen-2, AlignGVGD) do not provide strong support for or against an impact to the protein. Additional infor mation is needed to fully assess the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV003525865 SCV004283751 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2023-01-17 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2781 of the RYR2 protein (p.Thr2781Ser). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 165108). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR2 protein function. 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.

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