Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001967200 | SCV002206246 | uncertain significance | L-2-hydroxyglutaric aciduria | 2023-08-05 | 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. 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 L2HGDH protein function. ClinVar contains an entry for this variant (Variation ID: 1429237). This missense change has been observed in individual(s) with L-2-hydroxyglutaric aciduria (PMID: 19863265, 20052767; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs759631551, gnomAD 0.005%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 140 of the L2HGDH protein (p.Ala140Pro). |