Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001329379 | SCV001520811 | uncertain significance | L-2-hydroxyglutaric aciduria | 2020-12-18 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Invitae | RCV001329379 | SCV002225814 | uncertain significance | L-2-hydroxyglutaric aciduria | 2021-05-03 | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with L2HGDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1028351). This variant is present in population databases (rs763449413, ExAC 0.07%). This sequence change replaces isoleucine with threonine at codon 278 of the L2HGDH protein (p.Ile278Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |