Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003062630 | SCV003442332 | uncertain significance | L-2-hydroxyglutaric aciduria | 2022-01-04 | 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.Arg282 amino acid residue in L2HGDH. Other variant(s) that disrupt this residue have been observed in individuals with L2HGDH-related conditions (PMID: 18362286), 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 C15"). This missense change has been observed in individual(s) with L-2-hydroxyglutaric aciduria (PMID: 20052767). This variant is present in population databases (rs570111306, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 282 of the L2HGDH protein (p.Arg282Trp). |