Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
| Gene | IDH1 |
| Variant | F32V |
| Impact List | missense |
| Protein Effect | unknown |
| Gene Variant Descriptions | IDH1 F32V does not lie within any known functional domains of the Idh1 protein (UniProt.org). F32V has been identified in sequencing studies (PMID: 34160418, PMID: 37459200), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2024). |
| Associated Drug Resistance | |
| Category Variants Paths |
IDH1 mutant IDH1 F32V |
| Transcript | NM_005896.4 |
| gDNA | chr2:g.208251458A>C |
| cDNA | c.94T>G |
| Protein | p.F32V |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_005896.4 | chr2:g.208251458A>C | c.94T>G | p.F32V | RefSeq | GRCh38/hg38 |
| NM_001282386.1 | chr2:g.208251458A>C | c.94T>G | p.F32V | RefSeq | GRCh38/hg38 |
| NM_001282387.1 | chr2:g.208251458A>C | c.94T>G | p.F32V | RefSeq | GRCh38/hg38 |
| NM_001282386.1 | chr2:g.208251458A>C | c.94T>G | p.F32V | RefSeq | GRCh38/hg38 |
| NM_001282387.1 | chr2:g.208251458A>C | c.94T>G | p.F32V | RefSeq | GRCh38/hg38 |
| NM_005896.3 | chr2:g.208251458A>C | c.94T>G | p.F32V | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| IDH1 mutant | myelodysplastic syndrome | sensitive | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines for patients with myelodysplastic syndrome harboring an IDH1 mutation who progressed or failed to respond to prior treatment (NCCN.org). | detail... |
| IDH1 mutant | myelodysplastic syndrome | sensitive | Ivosidenib | FDA approved - Has 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 mutant | oligodendroglioma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | sensitive | Azacitidine + Ivosidenib | FDA approved - Has 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). | detail... 35443108 detail... |
| IDH1 mutant | acute myeloid leukemia | sensitive | Azacitidine + Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | sensitive | Cytarabine + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 72% (13/18) of patients with acute myeloid leukemia harboring IDH1 or IDH2 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). | detail... |
| IDH1 mutant | acute myeloid leukemia | sensitive | Cytarabine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | anaplastic astrocytoma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org). | detail... |
| IDH1 mutant | myeloid neoplasm | predicted - sensitive | Azacitidine + Ivosidenib + Venetoclax | Phase Ib/II | Actionable | In a Phase Ib/II trial, Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) and Venclexta (venetoclax) demonstrated safety and efficacy in patients with IDH1-mutant advanced myeloid malignancies, and led to a CRc (complete response (CR) + CR with partial hematologic recovery + CR with incomplete hematologic recovery) rate of 90% (17/19), 12-mo event-free survival (EFS) rate of 84%, 24-mo overall survival (OS) rate of 75%, and median EFS and OS were not reached (PMID: 37102976; NCT03471260). | 37102976 |
| IDH1 mutant | acute myeloid leukemia | sensitive | Azacitidine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | glioblastoma | not applicable | N/A | Clinical Study | Prognostic | In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with a greater overall survival and progression-free survival in patients with glioblastoma (PMID: 23904262, PMID: 26945349, PMID: 20560678). | 20560678 23904262 26945349 |
| IDH1 mutant | acute myeloid leukemia | sensitive | Azacitidine | Guideline | Actionable | Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | angioimmunoblastic T-cell lymphoma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
| IDH1 mutant | glioblastoma | predicted - sensitive | Bevacizumab + Lomustine | Phase II | Actionable | In a retrospective analysis of a Phase II trial, IDH1 mutation correlated with favorable overall survival in recurrent glioblastoma patients treated with a combination of Avastin (bevacizumab) and Lomustine (PMID: 26762204). | 26762204 |
| IDH1 mutant | high grade glioma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of gliomas (PMID: 23041832, PMID: 19755387, PMID: 19915484; NCCN.org). | detail... 23041832 19755387 19915484 |
| IDH1 mutant | high grade glioma | not applicable | N/A | Clinical Study | Prognostic | In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with improved overall survival and progression free survival in patients with gliomas (PMID: 23817809, PMID: 26220714, PMID: 23894344). | 23894344 23817809 26220714 |
| IDH1 mutant | high grade glioma | not applicable | N/A | Guideline | Prognostic | IDH1 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org). | detail... |
| IDH1 mutant | high grade glioma | no benefit | Durvalumab + Olaparib | Phase II | Actionable | In a Phase II trial, combination therapy with Lynparza (olaparib) and Imfinzi (durvalumab) was well tolerated, but lacked antitumor activity in glioma patients with IDH1 (8/9) or IDH2 (1/9) mutations, and led to an objective response in one patient with glioblastoma, stable disease as per RECIST but clinical deterioration in two patients, and progressive disease in 6/9 (67%) patients, with a median progression free survival of 2.5 mo (J Clin Oncol 39, no. 15_suppl (May 20, 2021) abstr e14026); NCT03991832). | detail... |
| IDH1 mutant | malignant astrocytoma | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | LY3410738 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, LY3410738 reversed mutant IDH1-induced differentiation block in patient-derived acute myeloid leukemia (AML) cells, inhibited 2-HG production, induced differentiation, and eliminated AML cells in patient-derived orthotopic animal models of IDH1-mutant AML (AACR 2019 Annual Meeting, Abstract LB-274). | detail... |
| IDH1 mutant | lung adenocarcinoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, lung adenocarcinoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123). | 27231123 |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH1 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
| IDH1 mutant | low grade glioma | predicted - sensitive | Vorasidenib | Phase I | Actionable | In a Phase I trial, Voranigo (vorasidenib) treatment resulted in an objective response in 13.6% (3/22, 1 partial response, 2 minor response) and stable disease in 72.7% (16/22) of patients with non-enhancing low-grade glioma harboring mutations in IDH1 (n=20) or IDH2 (n=1), with a median progression-free survival of 36.8 months, and resulted in stable disease as best response in 56.7% (17/30) of patients with enhancing tumors harboring mutations in IDH1 (n=28) or IDH2 (n=2) (PMID: 34078652; NCT02481154). | 34078652 |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Daunorubicin + Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination therapy of Lynparza (olaparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH1 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). | 29339439 |
| IDH1 mutant | chondrosarcoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, chondrosarcoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123). | 27231123 |
| IDH1 mutant | cholangiocarcinoma | sensitive | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in the Pan-Asian Guidelines Adaptation (PAGA) for cholangiocarcinoma patients harboring IDH1 mutations who have progressed after one or more lines of systemic therapy (PMID: 39232586; ESMO.org). | detail... 39232586 |
| IDH1 mutant | cholangiocarcinoma | sensitive | Ivosidenib | FDA approved - Has 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... detail... 32416072 |
| IDH1 mutant | cholangiocarcinoma | sensitive | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines as subsequent therapy (category 1) for cholangiocarcinoma patients harboring IDH1 mutations (NCCN.org). | detail... |
| IDH1 mutant | cholangiocarcinoma | sensitive | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines as second or later-line therapy for patients with cholangiocarcinoma harboring IDH1 mutations (PMID: 36372281; ESMO.org). | detail... 36372281 |
| IDH1 mutant | cholangiocarcinoma | sensitive | Ivosidenib | Phase I | Actionable | In a Phase I trial, AG-120 treatment resulted in partial response in 6% (4/72) and stable disease in 56% (40/72) of cholangiocarcinoma patients harboring IDH1 mutations (Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4015-4015; NCT02073994). | detail... |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Daunorubicin + Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination therapy of Talzenna (talazoparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH1 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). | 29339439 |
| IDH1 mutant | acute myeloid leukemia | sensitive | Olutasidenib | Guideline | Actionable | Rezlidhia (olutasidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | sensitive | Olutasidenib | FDA approved - Has 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 (R132C/G/H/L/S) (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7006; NCT02719574). | detail... detail... detail... |
| IDH1 mutant | high grade glioma | sensitive | Radiotherapy + Veliparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with Veliparib (ABT-888) enhanced the sensitivity of a glioma cell line xenograft model harboring an IDH1 mutation to radiation therapy, resulting in increased survival compared to radiation therapy alone, with a median overall survival of 21 days vs 14 days, respectively (PMID: 32494639). | 32494639 |
| IDH1 mutant | acute myeloid leukemia | not applicable | N/A | Clinical Study | Prognostic | In two meta-analyses, IDH1 mutations were associated with a worse overall survival in patients with acute myeloid leukemia (PMID: 22616558, PMID: 23226625). | 22616558 23226625 |
| IDH1 mutant | cholangiocarcinoma | no benefit | Durvalumab + Olaparib | Phase II | Actionable | In a Phase II trial, combination treatment with Lynparza (olaparib) and Imfinzi (durvalumab) was well tolerated but failed to demonstrate efficacy in patients with advanced cholangiocarcinoma harboring mutations in IDH1 or IDH2, with no objective responses, a disease control rate of 30% (3/10, 3 stable disease), and a median progression-free survival of 1.97 months (J Clin Oncol 41, 2023 (suppl 16; abstr 4099); NCT03991832). | detail... |
| IDH1 mutant | myeloid neoplasm | predicted - sensitive | Ivosidenib + Venetoclax | Phase Ib/II | Actionable | In a Phase Ib/II trial, combination treatment with Tibsovo (ivosidenib) and Venclexta (venetoclax) demonstrated safety and efficacy in patients with advanced myeloid malignancies harboring IDH1 mutations, and led to a CRc (complete response (CR) + CR with partial hematologic recovery + CR with incomplete hematologic recovery) rate of 83% (10/12), median event-free survival (EFS) of 11 mo, 12-mo EFS rate of 50%, median overall survival (OS) of 42.1 mo, and 24-mo OS rate of 58% (PMID: 37102976; NCT03471260). | 37102976 |
| IDH1 mutant | acute myeloid leukemia | sensitive | Ivosidenib | FDA approved - Has 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... 29860938 |
| IDH1 mutant | acute myeloid leukemia | sensitive | Ivosidenib | Guideline | Actionable | Tibsovo (ivosidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | predicted - sensitive | Venetoclax | Phase II | Actionable | In a Phase II trial, 33% (4/12) of acute myeloid leukemia patients harboring either IDH1 or IDH2 mutations responded to treatment with Venclexta (venetoclax), demonstrating a complete response or complete response with incomplete blood count recovery (PMID: 27520294). | 27520294 |
| IDH1 mutant | acute myeloid leukemia | sensitive | Decitabine | Guideline | Actionable | Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | polycythemia vera | not applicable | N/A | Guideline | Prognostic | IDH1 mutations are associated with inferior overall survival in patients with polycythemia vera (NCCN.org). | detail... |
| IDH1 mutant | acute myeloid leukemia | sensitive | Decitabine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org). | detail... |
| IDH1 mutant | myelofibrosis | not applicable | N/A | Guideline | Prognostic | IDH1 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org). | detail... |
| IDH1 mutant | myelofibrosis | not applicable | N/A | Guideline | Diagnostic | IDH1 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org). | detail... |
| IDH1 mutant | high grade glioma | sensitive | Olaparib + Radiotherapy | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Lynparza (olaparib) enhanced the sensitivity of a glioma cell line harboring an IDH1 mutation to radiation therapy in culture, resulting in decreased survival compared to radiation therapy alone (PMID: 32494639). | 32494639 |