Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000704273 | SCV000833215 | uncertain significance | RYR1-related disorder | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with valine at codon 402 of the RYR1 protein (p.Met402Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs766763626, ExAC 0.006%). 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: 580665). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant disrupts the p.Arg407 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17033962, 17483490, 20583297). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Fulgent Genetics, |
RCV002507235 | SCV002817027 | 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 | 2021-10-16 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV003130018 | SCV003814466 | uncertain significance | not provided | 2022-12-19 | criteria provided, single submitter | clinical testing |