Gene Variant Detail

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Gene IDH1
Variant R132C
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions IDH1 R132C lies within the active site of the Idh1 protein (PMID: 19228619). R132C confers a gain of function to Idh1 as indicated by conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate in culture (PMID: 19935646, PMID: 26161668, PMID: 22885298).
Associated Drug Resistance

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Transcript NM_005896
gDNA chr2:g.208248389G>A
cDNA c.394C>T
Protein p.R132C
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001282386 chr2:g.208248389G>A c.394C>T p.R132C RefSeq GRCh38/hg38
NM_005896 chr2:g.208248389G>A c.394C>T p.R132C RefSeq GRCh38/hg38
NM_001282387 chr2:g.208248389G>A c.394C>T p.R132C RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Protein Effect Treatment Approaches
IDH1 R132C gain of function IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 R132C SRC T341I
IDH1 R132C IDH1 S280F
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH1 R132C malignant glioma sensitive Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132C demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123). 27231123
IDH1 R132C acute myeloid leukemia sensitive Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839). detail... 29860938 detail...
IDH1 R132C acute myeloid leukemia sensitive Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839). detail... detail... detail... 29860938
IDH1 R132C sarcoma decreased response AGI-5198 + Olaparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C fibrosarcoma predicted - sensitive AG-881 Preclinical - Cell line xenograft Actionable In a preclinical study, AG-881 treatment decreased tumor 2HG levels in a fibrosarcoma cell line xenograft model harboring IDH1 R132C (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). detail...
IDH1 R132C intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth of intrahepatic cholangiocarcinoma cells harboring IDH1 R132C in culture, and suppressed tumor growth in PDX models (PMID: 27231123). 27231123
IDH1 R132C sarcoma sensitive Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, Lynparza (olaparib) treatment delayed tumor growth in cell line xenograft models of sarcoma harboring IDH1 R132C (PMID: 28148839). 28148839
IDH1 R132C chondrosarcoma predicted - sensitive Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132C (n=13) (PMID: 32208957; NCT02073994). 32208957
IDH1 R132C acute myeloid leukemia sensitive BAY1436032 Preclinical - Pdx & cell culture Actionable In a preclinical study, BAY1436032 decreased R-2HG levels and inhibited growth of primary acute myeloid leukemia (AML) cells harboring IDH1 R132C in culture, and decreased blast number and increased survival of two AML patient-derived xenograft (PDX) models, one which harbored additional alterations in FLT3, NPM1, and NRAS and one which harbored a KMT2A (MLL) alteration (PMID: 28232670). 28232670
IDH1 R132C malignant glioma sensitive AGI-5198 Preclinical Actionable In a preclinical study, AGI-5198 inhibited growth and promoted differentiation in glioma cells expressing IDH1 R132C (PMID: 23558169). 23558169
IDH1 R132C sarcoma decreased response AGI-5198 + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C SRC T341I intrahepatic cholangiocarcinoma resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S acquired resistance to Sprycel (dasatinib) after over expressing SRC T341I in culture (PMID: 27231123). 27231123
IDH1 R132C IDH1 S280F acute myeloid leukemia predicted - resistant Ivosidenib Case Reports/Case Series Actionable In a clinical study, IDH1 S280F was identified as an acquired mutation in cis with the original IDH1 R132C in a patient with acute myeloid leukemia (AML), who developed resistance to Tibsovo (ivosidenib) after initial response (PMID: 29950729). 29950729