Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003027922 | SCV003342549 | pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2022-06-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met497Cysfs*26) in the TBC1D24 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the TBC1D24 protein. This variant disrupts a region of the TBC1D24 protein in which other variant(s) (p.Ala515Val) have been determined to be pathogenic (PMID: 20727515, 26668325, 27281533, 31112829; Invitae). 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. |