Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000001932 | SCV003525084 | uncertain significance | D-2-hydroxyglutaric aciduria 1 | 2022-08-23 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects D2HGDH function (PMID: 30908763, 33431826). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 1858). This missense change has been observed in individual(s) with D-2-hydroxyglutaric aciduria (PMID: 16081310). 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 (rs267606759, gnomAD 0.02%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 375 of the D2HGDH protein (p.Asp375Tyr). 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. |
| OMIM | RCV000001932 | SCV000022090 | pathogenic | D-2-hydroxyglutaric aciduria 1 | 2005-09-01 | no assertion criteria provided | literature only |