Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001915156 | SCV002168064 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 389 of the TBC1D24 protein (p.His389Arg). This variant is present in population databases (rs528162903, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. ClinVar contains an entry for this variant (Variation ID: 1398636). 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 TBC1D24 protein function with a negative predictive value of 80%. 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. |