Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145803 | SCV000192940 | pathogenic | D-2-hydroxyglutaric aciduria 1 | 2014-05-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000145803 | SCV001389788 | uncertain significance | D-2-hydroxyglutaric aciduria 1 | 2022-07-05 | criteria provided, single submitter | clinical testing | 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. 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. Experimental studies have shown that this missense change affects D2HGDH function (PMID: 30908763, 33431826). ClinVar contains an entry for this variant (Variation ID: 158422). This missense change has been observed in individual(s) with D-2-hydroxyglutaric aciduria (PMID: 20020533). This variant is present in population databases (rs587783517, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 189 of the D2HGDH protein (p.Pro189Leu). |