ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9796A>T (p.Met3266Leu)

dbSNP: rs201588259
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001368477 SCV001564872 uncertain significance RYR1-related disorder 2021-08-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002476680 SCV002787961 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 2021-09-22 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003132478 SCV003810494 uncertain significance not provided 2019-09-18 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004006811 SCV004823916 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces methionine with leucine at codon 3266 of the RYR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 4/250522 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.
PreventionGenetics, part of Exact Sciences RCV001368477 SCV005344856 uncertain significance RYR1-related disorder 2024-03-06 no assertion criteria provided clinical testing The RYR1 c.9796A>T variant is predicted to result in the amino acid substitution p.Met3266Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0035% of alleles in individuals of European (Non-Finnish) descent in gnomAD. A different nucleotide change resulting in the same amino acid substitution has been reported in a patient with rhabdomyolysis-myalgia syndrome (c.9796A>C; Witting et al. 2018. PubMed ID: 29635721, Janssens et al. 2022. PubMed ID: 36283893). Evidence supporting pathogenicity were not provided. At this time, the clinical significance of the c.9796A>T variant is uncertain due to the absence of conclusive functional and genetic evidence.

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