ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.8342T>C (p.Ile2781Thr)

gnomAD frequency: 0.00007  dbSNP: rs767805554
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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 RCV001051646 SCV001215814 likely benign RYR1-related disorder 2024-01-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002505599 SCV002810117 likely benign Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-07-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV001051646 SCV004105089 uncertain significance RYR1-related disorder 2022-12-23 criteria provided, single submitter clinical testing The RYR1 c.8342T>C variant is predicted to result in the amino acid substitution p.Ile2781Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.054% of alleles in individuals of Latino descent in gnomAD including one homozygous individual (http://gnomad.broadinstitute.org/variant/19-38995980-T-C). Although we suspect this variant is benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Revvity Omics, Revvity RCV003490034 SCV004236891 uncertain significance not provided 2023-05-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003514460 SCV004358152 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-05-08 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 2781 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 24/280898 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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