Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000612105 | SCV000712810 | uncertain significance | not specified | 2017-03-20 | criteria provided, single submitter | clinical testing | The p.Ser492Phe variant in TBC1D24 has been previously reported by our laborator y in one individual with hearing loss. Data from large population studies are in sufficient to assess the frequency of this variant in the general population. C omputational prediction tools and conservation analyses do not provide strong su pport for or against an impact to the protein. In summary, the clinical signific ance of the p.Ser492Phe variant is uncertain. |
Invitae | RCV003767452 | SCV004576122 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 492 of the TBC1D24 protein (p.Ser492Phe). This variant is not present in population databases (gnomAD no frequency). 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: 505527). 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 expected to disrupt TBC1D24 protein function with a positive 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. |