Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001040303 | SCV001203866 | likely pathogenic | RYR1-related disorder | 2024-05-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 215 of the RYR1 protein (p.Gly215Arg). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of autosomal recessive RYR1-related myopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 838708). 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.Gly215 amino acid residue in RYR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12937085, 24319099). 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, |
RCV003130109 | SCV003814484 | uncertain significance | not provided | 2019-10-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004004731 | SCV004828534 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2024-06-09 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 215 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. his variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar variation ID: 838708). This variant has been identified in 2/282844 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia. |