Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825544 | SCV000966861 | likely pathogenic | Central core myopathy | 2018-03-12 | criteria provided, single submitter | clinical testing | The p.Gln764X variant in RYR1 has not been reported in individuals with myopathy , but has been identified in 1/111,698 European chromosomes by the Genome Aggreg ation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs371455345). Th is nonsense variant leads to a premature termination codon at position 764, and is predicted to lead to a truncated or absent protein. Loss of function of the R YR1 gene is associated with myopathy, including central core disease, multi-mini core disease, centronuclear myopathy, and congenital fiber type disproportion. I n summary, although additional studies are required to fully establish its clini cal significance, the p.Gln764X variant is likely pathogenic for RYR1-related my opathy in an autosomal recessive manner. ACMG/AMP Criteria applied: PVS1, PM2. |
| Labcorp Genetics |
RCV001383922 | SCV001583250 | pathogenic | RYR1-related disorder | 2020-04-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 666984). This variant is present in population databases (rs371455345, ExAC 0.001%). This sequence change creates a premature translational stop signal (p.Gln764*) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 20583297, 20839240, 23919265, 28818389). For these reasons, this variant has been classified as Pathogenic. |