ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.2449C>G (p.Pro817Ala)

dbSNP: rs780266883
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000176274 SCV000227904 uncertain significance not provided 2015-04-08 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000778017 SCV000914127 uncertain significance Cardiomyopathy 2023-01-03 criteria provided, single submitter clinical testing This missense variant replaces proline with alanine at codon 817 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). Computational splicing tools suggest that this variant may impact the RNA splicing. 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 18/248932 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.
Invitae RCV002516704 SCV001680128 likely benign Catecholaminergic polymorphic ventricular tachycardia 1 2023-02-16 criteria provided, single submitter clinical testing
GeneDx RCV000176274 SCV003924696 uncertain significance not provided 2023-05-11 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not 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); At the protein level, in silico analysis supports that this missense variant has a deleterious effect on protein structure/function; At the mRNA level, in silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 19926015)

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