ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9586C>T (p.Arg3196Cys)

gnomAD frequency: 0.00003  dbSNP: rs766362010
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001228143 SCV001400528 uncertain significance RYR1-Related Disorders 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 3196 of the RYR1 protein (p.Arg3196Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs766362010, ExAC 0.02%). 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002491721 SCV002775431 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-08-24 criteria provided, single submitter clinical testing
GeneDx RCV003238849 SCV003936206 uncertain significance not provided 2023-07-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 12668474)

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