ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9277C>T (p.Arg3093Cys)

dbSNP: rs1064797039
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000535216 SCV000660086 uncertain significance RYR1-related disorder 2021-08-28 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). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000764192 SCV000895195 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion 2018-10-31 criteria provided, single submitter clinical testing

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