ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13628G>C (p.Gly4543Ala)

dbSNP: rs200002274
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532059 SCV000659822 uncertain significance RYR1-related disorder 2022-03-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 4543 of the RYR1 protein (p.Gly4543Ala). This variant is present in population databases (rs200002274, gnomAD 0.02%). 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: 478186). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
PreventionGenetics, part of Exact Sciences RCV000721325 SCV000852358 uncertain significance not provided 2015-07-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002491115 SCV002775590 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 2021-09-10 criteria provided, single submitter clinical testing
GeneDx RCV000721325 SCV003919540 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
All of Us Research Program, National Institutes of Health RCV003999486 SCV004839366 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-12-06 criteria provided, single submitter clinical testing

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