ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.10817T>C (p.Leu3606Pro)

dbSNP: rs118192127
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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 RCV005089462 SCV005837968 likely pathogenic RYR1-related disorder 2024-04-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3606 of the RYR1 protein (p.Leu3606Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive RYR1-related conditions (PMID: 16621918, 27363342). ClinVar contains an entry for this variant (Variation ID: 65958). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneReviews RCV000056205 SCV000087294 pathologic Central core myopathy 2010-05-11 no assertion criteria provided curation Converted during submission to Pathogenic.
RYR1 database RCV000119419 SCV000154326 not provided not provided no assertion provided not provided

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