ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.10049G>A (p.Arg3350Gln)

gnomAD frequency: 0.00001  dbSNP: rs538500669
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001093153 SCV001250000 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001231239 SCV001403752 uncertain significance RYR1-related disorder 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 3350 of the RYR1 protein (p.Arg3350Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs538500669, ExAC 0.006%). 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 RCV002482167 SCV002785806 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 2021-09-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000222 SCV004820966 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-05-30 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 3350 of the RYR1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 2/251052 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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