Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001218892 | SCV001390800 | uncertain significance | L-2-hydroxyglutaric aciduria | 2019-10-09 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Gly260 amino acid residue in L2HGDH. Other variant(s) that disrupt this residue have been observed in individuals with L2HGDH-related conditions (PMID: 20052767, 22030381), which suggests that this may be a clinically significant amino acid residue. 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 C0"). This variant has been observed in an individual affected with L-2-hydroxyglutaric aciduria (PMID: 20052767). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 260 of the L2HGDH protein (p.Gly260Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |