ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.638G>A (p.Ser213Asn)

dbSNP: rs1702026122
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183201 SCV001348859 uncertain significance Cardiomyopathy 2020-03-06 criteria provided, single submitter clinical testing This missense variant replaces serine with asparagine at codon 213 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 not been identified 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.
Invitae RCV002559046 SCV001387517 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2020-01-23 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 213 of the RYR2 protein (p.Ser213Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. 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. 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RYR2-related conditions.

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