ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8027T>C (p.Leu2676Ser)

gnomAD frequency: 0.00001  dbSNP: rs1338788038
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002552079 SCV001198411 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-02-01 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 834415). 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 leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2676 of the RYR2 protein (p.Leu2676Ser).
Color Diagnostics, LLC DBA Color Health RCV001524514 SCV001734401 uncertain significance Cardiomyopathy 2023-03-16 criteria provided, single submitter clinical testing This missense variant replaces leucine with serine at codon 2676 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 1/242718 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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