Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236040 | SCV001408752 | uncertain significance | RYR1-related disorder | 2022-05-06 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2544 of the RYR1 protein (p.Thr2544Ser). This variant is present in population databases (rs146326299, gnomAD 0.007%). This missense change has been observed in individual(s) with Hypotonia, muscle weakness, and developmental delay since infancy (Invitae). ClinVar contains an entry for this variant (Variation ID: 962225). 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, |
RCV002480770 | SCV002775637 | 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 | 2022-04-19 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004004865 | SCV004820918 | uncertain significance | Malignant hyperthermia, susceptibility to, 1 | 2024-01-22 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with serine at codon 2544 of the RYR1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with malignant hyperthermia susceptibility, although it has been reported in an individual affected with a different condition (ClinVar: SCV001408752.4). This variant has been identified in 7/246000 chromosomes 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. |