Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000813854 | SCV000954235 | uncertain significance | D-2-hydroxyglutaric aciduria 2 | 2018-10-18 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs771346231, ExAC 0.003%). This sequence change replaces lysine with glutamic acid at codon 282 of the IDH2 protein (p.Lys282Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant has not been reported in the literature in individuals with IDH2-related disease. 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: "Benign"; Align-GVGD: "Class C55"). 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. |
Clinical Genomics Laboratory, |
RCV003456437 | SCV004176987 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | The IDH2 c.844A>G (p.Lys282Glu) variant was identified at a near heterozygous allelic fraction. This variant, to our knowledge, has not been reported in the medical literature. This variant has been reported in the ClinVar database as a variant of uncertain significance by one submitter (ClinVar Variantion ID: 657276), and in one case in the cancer database COSMIC (Genomic Mutation ID: COSV57473516). Computational predictors are uncertain as to the impact of this variant on 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. |