Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001212453 | SCV001384036 | likely pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2023-06-16 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Arg65 amino acid residue in TBC1D24. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30139988). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 942461). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (rs750421791, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 65 of the TBC1D24 protein (p.Arg65Cys). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV001586055 | SCV001812976 | uncertain significance | not provided | 2021-03-23 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002411784 | SCV002720832 | uncertain significance | Inborn genetic diseases | 2018-05-02 | criteria provided, single submitter | clinical testing | The p.R65C variant (also known as c.193C>T), located in coding exon 1 of the TBC1D24 gene, results from a C to T substitution at nucleotide position 193. The arginine at codon 65 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |