ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.499A>G (p.Lys167Glu) (rs794728707)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182657 SCV000235035 likely pathogenic not provided 2017-08-30 criteria provided, single submitter clinical testing The K167E likely pathogenic variant in the RYR2 gene has not been published as pathogenic nor has it been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The K176E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved across species and is 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). Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Finally, missense variants in nearby residues (A165D, S166C, R169L, R169Q) have been reported in the Human Gene Mutation Database in association with arrhythmia (Stenson et al., 2014), further supporting the functional importance of this region of the protein.

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