Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001212729 | SCV001384323 | uncertain significance | D-2-hydroxyglutaric aciduria 1 | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 247 of the D2HGDH protein (p.Thr247Met). This variant is present in population databases (rs768774887, 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: 942698). 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. |
Ambry Genetics | RCV002561794 | SCV003548886 | uncertain significance | Inborn genetic diseases | 2021-05-24 | criteria provided, single submitter | clinical testing | The c.740C>T (p.T247M) alteration is located in exon 6 (coding exon 5) of the D2HGDH gene. This alteration results from a C to T substitution at nucleotide position 740, causing the threonine (T) at amino acid position 247 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |