ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1172G>A (p.Arg391His)

gnomAD frequency: 0.00006  dbSNP: rs769387053
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000721249 SCV000225530 uncertain significance not provided 2014-12-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000721249 SCV000852266 uncertain significance not provided 2016-03-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000808818 SCV000948940 uncertain significance RYR1-related disorder 2022-03-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 391 of the RYR1 protein (p.Arg391His). This variant is present in population databases (rs769387053, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 194002). 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: "Probably 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.
Genetic Services Laboratory, University of Chicago RCV001818418 SCV002065502 uncertain significance not specified 2017-12-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002478561 SCV002794342 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 2021-08-19 criteria provided, single submitter clinical testing
GeneDx RCV000721249 SCV004023109 uncertain significance not provided 2023-01-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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