Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001994540 | SCV002234609 | pathogenic | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg724*) in the MUSK gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 146 amino acid(s) of the MUSK protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1452397). This variant disrupts a region of the MUSK protein in which other variant(s) (p.Val790) have been determined to be pathogenic (PMID: 15496425, 23326516, 24122059, 30429133). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |