Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003870084 | SCV004673737 | pathogenic | Congenital myasthenic syndrome 4A | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp460*) in the CHRNE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acid(s) of the CHRNE protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the CHRNE protein in which other variant(s) (p.Trp460*) have been determined to be pathogenic (PMID: 12417530). 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. |