ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.14884T>A (p.Tyr4962Asn) (rs748937501)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182855 SCV000235243 likely pathogenic not provided 2017-05-04 criteria provided, single submitter clinical testing The Y4962N likely pathogenic variant in the RYR2 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Y4962N variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y4962N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Moreover, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. One missense variant in the same residue (Y4962C) has been reported in the Human Gene Mutation Database in association with CPVT (Stenson et al., 2014); however, the pathogenicity of this variant has not been definitively determined. Finally, the Y4962N variant is located in close proximity to one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros- Domingo et al., 2009).

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