ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.10922T>C (p.Ile3641Thr)

dbSNP: rs1060500145
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002522773 SCV000541667 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3641 of the RYR2 protein (p.Ile3641Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). 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 RCV001181130 SCV001346216 uncertain significance Cardiomyopathy 2020-01-29 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 3641 of the RYR2 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold ≥0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.

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