Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003460052 | SCV004192827 | uncertain significance | Exostoses, multiple, type 2 | 2023-07-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003460052 | SCV004533706 | uncertain significance | Exostoses, multiple, type 2 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 339 of the EXT2 protein (p.Cys339Ser). This variant is present in population databases (rs751598619, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. 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 EXT2 protein function. This variant disrupts the p.Cys339 amino acid residue in EXT2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19839753, 26961984, 30334991, 30806661). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |