ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.82C>T (p.Leu28Phe)

gnomAD frequency: 0.00001  dbSNP: rs1242495143
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655549 SCV000777480 uncertain significance RYR1-related disorder 2018-02-06 criteria provided, single submitter clinical testing 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. This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RYR1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 28 of the RYR1 protein (p.Leu28Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine.
Fulgent Genetics, Fulgent Genetics RCV002507139 SCV002813341 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 2021-10-29 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003129980 SCV003814348 uncertain significance not provided 2019-01-04 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV000655549 SCV004037549 not provided RYR1-related disorder no assertion provided phenotyping only Variant classified as Uncertain significance and reported on 11-27-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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