ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9615C>G (p.Phe3205Leu)

gnomAD frequency: 0.00001  dbSNP: rs1223136232
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000516312 SCV000614918 uncertain significance not specified 2017-03-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001232037 SCV001404580 uncertain significance RYR1-related disorder 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3205 of the RYR1 protein (p.Phe3205Leu). This variant is present in population databases (no rsID available, 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: 448183). 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 expected to disrupt RYR1 protein function with a positive predictive value of 95%. 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.
GeneDx RCV001755771 SCV001996494 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016)
Fulgent Genetics, Fulgent Genetics RCV002481683 SCV002794362 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 2021-08-30 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001755771 SCV003814480 uncertain significance not provided 2019-05-20 criteria provided, single submitter clinical testing

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