ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.3679A>G (p.Ile1227Val)

gnomAD frequency: 0.00001  dbSNP: rs746166976
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001263010 SCV001441082 uncertain significance Malignant hyperthermia, susceptibility to, 1 2019-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001880052 SCV002234070 uncertain significance RYR1-related disorder 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1227 of the RYR1 protein (p.Ile1227Val). This variant is present in population databases (rs746166976, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of RYR1-related conditions (PMID: 30325262). ClinVar contains an entry for this variant (Variation ID: 983142). 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 not expected to disrupt RYR1 protein function with a negative 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.
All of Us Research Program, National Institutes of Health RCV001263010 SCV004820817 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-08-15 criteria provided, single submitter clinical testing

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