Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001960782 | SCV002241192 | uncertain significance | RYR1-related disorder | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 1763 of the RYR1 protein (p.Pro1763Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with hyperCKemia (PMID: 31517061). 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 not 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. |
| Fulgent Genetics, |
RCV002507712 | SCV002812268 | 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 | 2021-07-30 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004808173 | SCV005431036 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2024-08-23 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 1763 of the RYR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hyperCKemia (PMID: 31517061). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |