ClinVar Miner

Submissions for variant NM_002168.3(IDH2):c.419G>A (p.Arg140Gln) (rs121913502)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000015831 SCV000807283 pathogenic D-2-hydroxyglutaric aciduria 2 2017-09-01 criteria provided, single submitter clinical testing This mutation has been previously reported as disease-causing and was found once in our laboratory de novo and mosaic in a 2-year-old male with motor delays, absent speech, hypertonia, epilepsy, short statures, failure to thrive, vision loss, MRI suggestive of Leigh disease
Database of Curated Mutations (DoCM) RCV000419192 SCV000504572 pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431189 SCV000504573 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441454 SCV000504574 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420290 SCV000504575 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430530 SCV000504576 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
GeneDx RCV000292094 SCV000329950 pathogenic not provided 2018-05-24 criteria provided, single submitter clinical testing The R140Q pathogenic variant in the IDH2 gene has been reported previously as a de novo variant in the heterozygous state in multiple individuals with D-2 hydroxyglutaric aciduria type 2 (Kranendijk et al., 2010). R140Q has also been reported as de novo in the mosaic state in an individual with D-2HGA type 2. In addition, R140Q was also reported as mosaic in the unaffected mother of an individual with D-2HGA type 2 (Kranendijk et al., 2010; Nota et al., 2013). The R140Q variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R140Q variant is a semi-conservative amino acid substitution, which occurs as a position that is conserved across species. An enzyme assay which determines IDH2 activity in lymphoblast extracts was created, and confirmed that R140Q results in gain of function in D-2 hydroxyglutaric aciduria type 2 (Kranendijk et al., 2011). We interpret R140Q as a pathogenic variant.
Genetic Services Laboratory, University of Chicago RCV000015831 SCV000247596 pathogenic D-2-hydroxyglutaric aciduria 2 2014-12-11 criteria provided, single submitter clinical testing
OMIM RCV000015831 SCV000036098 pathogenic D-2-hydroxyglutaric aciduria 2 2013-11-01 no assertion criteria provided literature only

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