ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4235A>G (p.Asp1412Gly)

dbSNP: rs1553515461
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV004760637 SCV005369083 uncertain significance not provided 2023-06-21 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; 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)
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV000584816 SCV000692520 uncertain significance Brugada syndrome 2020-04-07 no assertion criteria provided research The RYR2 Asp1412Gly is a novel variant. It is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified the RYR2 Asp1412Gly variant in a proband presenting with cardiac arrest, who was subsequently diagnosed with Brugada Syndrome (type 1 ECG). The proband has no family history of disease or SCD. Computational tools SIFT and MutationTaster predict this variant to be "deleterious" and "disease-causing" respectively, however PolyPhen-2 predicts the variant to be "benign". Based on the limited information available and rarity in general populations, we classify RYR2 Asp1412Gly as a variant of "uncertain significance".

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