ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12215C>T (p.Thr4072Met)

gnomAD frequency: 0.00002  dbSNP: rs928224285
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002523284 SCV000541727 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2023-12-21 criteria provided, single submitter clinical testing
GeneDx RCV000489632 SCV000576527 uncertain significance not provided 2023-09-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009)
Color Diagnostics, LLC DBA Color Health RCV000772023 SCV000904979 uncertain significance Cardiomyopathy 2023-09-08 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 4072 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). 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 10/278420 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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