ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.5384C>T (p.Pro1795Leu)

gnomAD frequency: 0.00006  dbSNP: rs141379562
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001945381 SCV002190547 uncertain significance RYR1-related disorder 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1795 of the RYR1 protein (p.Pro1795Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs141379562, ExAC 0.05%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV002484492 SCV002787716 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 2021-09-13 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010872 SCV004819726 uncertain significance Malignant hyperthermia, susceptibility to, 1 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 1795 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 11/271280 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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