ClinVar Miner

Submissions for variant NM_002168.4(IDH2):c.923G>C (p.Cys308Ser)

dbSNP: rs1344620365
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220415 SCV001392403 uncertain significance D-2-hydroxyglutaric aciduria 2 2022-03-15 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 949037). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with IDH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 308 of the IDH2 protein (p.Cys308Ser).
Clinical Genomics Laboratory, Washington University in St. Louis RCV001220415 SCV005685288 uncertain significance D-2-hydroxyglutaric aciduria 2 2024-05-16 criteria provided, single submitter clinical testing The IDH2 c.923G>C (p.Cys308Ser) variant was identified at a near heterozygous allelic fraction of 48.7%, a frequency which may be consistent with it being of germline origin. This variant, to our knowledge, has not been reported in the medical literature and it is absent from the general population (gnomAD v.4.1.0), indicating it is not a common variant. This variant has been reported in the ClinVar database as a variant of uncertain significance by one submitter (ClinVar ID: 949037). Computational predictors indicate that the variant is damaging, evidence that correlates with impact to IDH2 function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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