Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002654900 | SCV003521307 | uncertain significance | L-2-hydroxyglutaric aciduria | 2022-10-17 | 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.Ala62Asp amino acid residue in L2HGDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18780161, 25033591). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 62 of the L2HGDH protein (p.Ala62Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. |