ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4753C>T (p.Arg1585Cys)

gnomAD frequency: 0.00001  dbSNP: rs528206995
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002554446 SCV001227477 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1585 of the RYR2 protein (p.Arg1585Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs528206995, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. 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. 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 Diagnostics, LLC DBA Color Health RCV001179255 SCV001343866 uncertain significance Cardiomyopathy 2023-11-10 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 1585 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 RYR2-related disorders in the literature. This variant has been identified in 4/246796 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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