ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.9277C>T (p.Arg3093Cys) (rs1064797039)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764192 SCV000895195 uncertain significance Myopathy, Central Core; Malignant hyperthermia, susceptibility to, 1; Minicore myopathy; Congenital myopathy with fiber type disproportion 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000482428 SCV000574373 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing The R3093C variant in the RYR1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R3093C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R3093C 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R3093C as a variant of uncertain significance.
Invitae RCV000535216 SCV000660086 uncertain significance RYR1-Related Disorders 2017-08-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 3093 of the RYR1 protein (p.Arg3093Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RYR1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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