Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000698657 | SCV000827337 | uncertain significance | L-2-hydroxyglutaric aciduria | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 24 of the L2HGDH protein (p.Pro24Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Athena Diagnostics Inc | RCV001662770 | SCV001880681 | uncertain significance | not provided | 2020-11-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002533535 | SCV003671117 | likely benign | Inborn genetic diseases | 2022-12-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |