Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001322380 | SCV001513248 | pathogenic | D-2-hydroxyglutaric aciduria 1 | 2022-10-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the D2HGDH protein in which other variant(s) (p.Ala474Val) have been determined to be pathogenic (PMID: 30908763, 33431826; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1022469). This variant has not been reported in the literature in individuals affected with D2HGDH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the D2HGDH gene (p.Thr465Argfs*215). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 57 amino acid(s) of the D2HGDH protein and extend the protein by 157 additional amino acid residues. |