ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.4718C>T (p.Pro1573Leu)

gnomAD frequency: 0.00001  dbSNP: rs774364705
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001562543 SCV001785323 uncertain significance not provided 2021-04-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22407809)
Labcorp Genetics (formerly Invitae), Labcorp RCV002570736 SCV003443236 uncertain significance RYR1-related disorder 2022-03-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1573 of the RYR1 protein (p.Pro1573Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with autosomal recessive RYR1-related conditions (PMID: 22407809). ClinVar contains an entry for this variant (Variation ID: 1198404). 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. 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 RCV004008934 SCV004823188 uncertain significance Malignant hyperthermia, susceptibility to, 1 2022-12-07 criteria provided, single submitter clinical testing

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