Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002023302 | SCV002305368 | likely pathogenic | Alkaptonuria | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 225 of the HGD protein (p.Arg225Cys). This variant is present in population databases (rs756789146, gnomAD 0.007%). This missense change has been observed in individual(s) with alkaptonuria (Invitae). ClinVar contains an entry for this variant (Variation ID: 1512988). 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 HGD protein function with a positive predictive value of 80%. This variant disrupts the p.Arg225 amino acid residue in HGD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12872836, 25681086). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Department Of Human Genetics, |
RCV002023302 | SCV004101002 | pathogenic | Alkaptonuria | no assertion criteria provided | research | The variant was originally described in AKU patient in https://doi.org/10.3934/molsci.2021005. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00254). |