ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.4847C>T (p.Thr1616Met) (rs776194441)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000765447 SCV000896738 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
Invitae RCV000541033 SCV000659946 uncertain significance RYR1-Related Disorders 2017-11-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1616 of the RYR1 protein (p.Thr1616Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs776194441, ExAC 0.4%) but 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 rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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