ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.349C>T (p.His117Tyr) (rs1057524592)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439111 SCV000535990 uncertain significance not provided 2017-01-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR2 gene. The H117Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H117Y 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 in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, H117Y 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). Nevertheless, this variant has not been observed in a significant number of affected individuals, and there are no functional or segregation studies available to further clarify the role of this variant in disease.

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