Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000696311 | SCV000824864 | uncertain significance | Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 | 2020-01-04 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Ala244 amino acid residue in TBC1D24. Other variant(s) that disrupt this residue have been observed in individuals with TBC1D24-related conditions (PMID: 27281533, 28072960), which suggests that this may be a clinically significant amino acid residue. 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. This variant has not been reported in the literature in individuals with TBC1D24-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glutamic acid at codon 244 of the TBC1D24 protein (p.Ala244Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. |