Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001040954 | SCV001204547 | pathogenic | RYR1-related disorder | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 4825 of the RYR1 protein (p.Arg4825His). This variant is present in population databases (rs193922875, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal dominant malignant hyperthermia susceptibility (PMID: 36283893). ClinVar contains an entry for this variant (Variation ID: 839243). 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.Arg4825Cys amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11709545, 17204937, 35081925, 35428369). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002481884 | SCV002794485 | 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 | 2021-09-14 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV003130110 | SCV003814453 | uncertain significance | not provided | 2022-11-16 | criteria provided, single submitter | clinical testing |