ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.4004G>A (p.Arg1335His)

gnomAD frequency: 0.00002  dbSNP: rs750256869
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693797 SCV000821680 uncertain significance RYR1-related disorder 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1335 of the RYR1 protein (p.Arg1335His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs750256869, ExAC 0.009%). 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: "Possibly Damaging"; 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 RCV002477570 SCV002790379 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 2021-09-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999602 SCV004814569 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-05-15 criteria provided, single submitter clinical testing

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