ClinVar Miner

Submissions for variant NM_001282386.1(IDH1):c.395G>A (p.Arg132His) (rs121913500)

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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000853347 SCV000996209 pathogenic Metaphyseal enchondromatosis with d-2-hydroxyglutaric aciduria 2018-11-02 criteria provided, single submitter clinical testing This variant has been previously reported as a mosaic change in patients with metaphyseal chondromatosis and elevated D-2-hydroxyglutaric aciduria (PMID: 24049096, 22025298). It is absent from the gnomAD population databases and thus is presumed to be rare. The c.395G>A, p.Arg132H variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. The p.Arg132H variant results in loss of its native enzymatic activity and gain of alternative enzymatic activity (producing D-2-hydroxyglutarate) (PMID 21446021). Structural studies demonstrated that when p.Arg132 is mutated to histidine (R132H), residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG (PMID 19935646). Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumors in patients with inborn errors of 2HG metabolism (PMID 18931888). Based on the available evidence, the c.395G>A, p.Arg132H variant is classified as Pathogenic.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV001269510 SCV001449548 pathogenic not provided 2019-10-29 criteria provided, single submitter clinical testing
OMIM RCV000144504 SCV000189823 pathogenic Glioblastoma multiforme, somatic 2014-08-21 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420454 SCV000503802 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431117 SCV000503803 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441845 SCV000503804 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419255 SCV000503805 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429987 SCV000503806 pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440637 SCV000503807 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423408 SCV000503808 likely pathogenic Medulloblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428884 SCV000503809 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439554 SCV000503810 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422344 SCV000503811 likely pathogenic Brainstem glioma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433068 SCV000503812 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442517 SCV000503813 likely pathogenic Astrocytoma 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421389 SCV000503814 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432047 SCV000503815 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445280 SCV000503816 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427239 SCV000503817 likely pathogenic Adenoid cystic carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423229 SCV000505707 not provided Oligodendroglioma 2016-03-10 no assertion provided literature only
Genomics England Pilot Project,Genomics England RCV001542733 SCV001760072 likely pathogenic Glioma susceptibility 1 no assertion criteria provided clinical testing

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