ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.14635C>A (p.Gln4879Lys) (rs730880200)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000157469 SCV000207214 likely pathogenic Paroxysmal familial ventricular fibrillation 1 2014-03-24 no assertion criteria provided clinical testing
GeneDx RCV000489644 SCV000576650 uncertain significance not provided 2017-04-24 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR2 gene. The Q4879K variant has not been published as pathogenic or 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 Q4879K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Moreover, the Q4879K variant 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). However, this variant has not been identified in a significant number of affected individuals, and there are no functional studies or segregation data available to clarify the role of this variant in disease.

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