Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001906294 | SCV002169995 | uncertain significance | L-2-hydroxyglutaric aciduria | 2021-11-23 | 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 tolerated. This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. This variant is present in population databases (rs540187537, gnomAD 0.04%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 183 of the L2HGDH protein (p.Met183Val). |
Ambry Genetics | RCV003339800 | SCV004066075 | uncertain significance | Inborn genetic diseases | 2023-08-08 | criteria provided, single submitter | clinical testing | The c.547A>G (p.M183V) alteration is located in exon 5 (coding exon 5) of the L2HGDH gene. This alteration results from a A to G substitution at nucleotide position 547, causing the methionine (M) at amino acid position 183 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |