Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000428266 | SCV000528163 | uncertain significance | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV001069475 | SCV001234642 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 485 of the TBC1D24 protein (p.Ala485Thr). This variant is present in population databases (rs774586263, gnomAD 0.03%). 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: 386478). 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 95%. 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. |
Ce |
RCV000428266 | SCV001501588 | uncertain significance | not provided | 2023-10-01 | criteria provided, single submitter | clinical testing | TBC1D24: PM2, BP4 |
Ambry Genetics | RCV002393011 | SCV002701893 | uncertain significance | Inborn genetic diseases | 2020-04-27 | criteria provided, single submitter | clinical testing | The p.A485T variant (also known as c.1453G>A), located in coding exon 6 of the TBC1D24 gene, results from a G to A substitution at nucleotide position 1453. The alanine at codon 485 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |