ClinVar Miner

Submissions for variant NM_024884.3(L2HGDH):c.70C>T (p.Pro24Ser)

gnomAD frequency: 0.00006  dbSNP: rs749417358
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Total submissions: 3
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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.

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