Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001035164 | SCV001198479 | uncertain significance | D-2-hydroxyglutaric aciduria 1 | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 347 of the D2HGDH protein (p.Ala347Thr). This variant is present in population databases (rs142624021, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with D2HGDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 834472). 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 not expected to disrupt D2HGDH protein function. 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. |
Baylor Genetics | RCV001035164 | SCV001526226 | uncertain significance | D-2-hydroxyglutaric aciduria 1 | 2018-11-16 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002552082 | SCV003680895 | uncertain significance | Inborn genetic diseases | 2021-05-25 | criteria provided, single submitter | clinical testing | The c.1039G>A (p.A347T) alteration is located in exon 8 (coding exon 7) of the D2HGDH gene. This alteration results from a G to A substitution at nucleotide position 1039, causing the alanine (A) at amino acid position 347 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |