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Gene IDH1
Variant R132L
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions IDH1 R132L lies within the active site of the Idh1 protein (PMID: 19228619). R132L confers a gain of function to Idh1, as indicated by increased conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 19935646, PMID: 21326614).
Associated Drug Resistance
Category Variants Paths

IDH1 mutant IDH1 act mut IDH1 R132L

IDH1 mutant IDH1 R132X IDH1 R132L

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Transcript NM_005896.4
gDNA chr2:g.208248388C>A
cDNA c.395G>T
Protein p.R132L
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_005896 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_001282386.1 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_005896.3 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_001282386.1 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_001282387.1 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_001282387 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_001282387.1 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_005896.4 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38
NM_001282386 chr2:g.208248388C>A c.395G>T p.R132L RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH1 R132L 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 R132L (n=1) (PMID: 32208957; NCT02073994). 32208957
IDH1 R132L cholangiocarcinoma sensitive Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857). detail... 32416072 detail...
IDH1 R132L 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). 29860938 detail... detail...
IDH1 R132L 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). 29860938 detail... detail...
IDH1 R132L myelodysplastic syndrome sensitive Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) was tolerated and resulted in a complete response (CR) in 44% (7/16), partial response (PR) in 6% (1/16), and marrow CR in 31% (5/16) of patients with relapsed or refractory myelodysplastic syndrome harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a hematologic improvement in >/=1 lineages achieved by 69% (11/16) of patients (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 7053; NCT02074839). detail... detail... detail...
IDH1 R132L acute myeloid leukemia sensitive Azacitidine + Ivosidenib Phase Ib/II Actionable In a Phase Ib trial, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination treatment demonstrated a favorable safety profile and resulted in an objective response rate (ORR) of 78.3% (18/23, 14 complete remission) and a 12-month overall survival probability of 82% in patients with newly diagnosed acute myeloid leukemia harboring IDH1 R132L (n=3), R132H (n=4), or R132C (n=16) mutations (PMID: 33119479; NCT02677922). 33119479
IDH1 R132L acute myeloid leukemia sensitive Azacitidine + Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination therapy significantly improved event-free survival (HR 0.33, p=0.002) and median overall survival (24.0 vs 7.9 mo, HR 0.44, p=0.001) compared to Vidaza (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248). 35443108 detail... detail...
IDH1 R132L acute myeloid leukemia sensitive Olutasidenib FDA approved - On Companion Diagnostic Actionable In a Phase II trial (Study 2102-HEM-101) that supported FDA approval, Rezlidhia (olutasidenib) treatment resulted in an objective response rate of 46% (57/123, 37 complete remission (CR), 4 CR with partial hematologic recovery, 14 CR with incomplete recovery, 1 morphologic leukemia-free state, 1 partial response) in patients with relapsed/refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132L/C/G/H/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574). detail... detail... detail...
IDH1 R132L acute myeloid leukemia sensitive BAY1436032 Preclinical - Patient cell culture Actionable In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132L in culture (PMID: 28232670). 28232670
IDH1 R132L Advanced Solid Tumor predicted - sensitive DS-1001b Preclinical - Biochemical Actionable In a preclinical study, transformed human cells expressing IDH1 R132L demonstrated sensitivity to DS-1001b in culture, resulting in reduced production of the oncometabolite 2-hydroxyglutarate (2-HG) (PMID: 31727689). 31727689