Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000996859 | SCV001151808 | uncertain significance | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001858845 | SCV002279862 | likely pathogenic | RYR1-Related Disorders | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 530 of the RYR1 protein (p.Arg530Cys). This variant is present in population databases (rs757399861, gnomAD 0.03%). 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: 808532). 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%. This variant disrupts the p.Arg530 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16917943, 19191329, 19191333, 26578207, 27646467). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Revvity Omics, |
RCV000996859 | SCV003814437 | uncertain significance | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing |