ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4991T>A (p.Val1664Asp)

dbSNP: rs878854158
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002516311 SCV000285733 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-09-23 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 238236). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1664 of the RYR2 protein (p.Val1664Asp). 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. 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 expected to disrupt RYR2 protein function.
Color Diagnostics, LLC DBA Color Health RCV003532065 SCV004360613 uncertain significance Cardiomyopathy 2022-05-26 criteria provided, single submitter clinical testing This missense variant replaces valine with aspartic acid at codon 1664 of the RYR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/249012 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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