ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.12962G>A (p.Arg4321Gln)

gnomAD frequency: 0.00001  dbSNP: rs1313365429
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000793163 SCV000932504 uncertain significance RYR1-related disorder 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 4321 of the RYR1 protein (p.Arg4321Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002501043 SCV002775462 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 2021-08-17 criteria provided, single submitter clinical testing

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