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Gene | IDH2 |
Variant | R172X |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | IDH2 R172X indicates any Idh2 missense mutation that results in the replacement of the arginine (R) at amino acid 172 by a different amino acid. R172 variants are hotspot mutations in Idh2, which may confer a gain of function to Idh2 resulting in conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) (PMID: 28711227, PMID: 21326614, PMID: 25495392). |
Associated Drug Resistance | |
Category Variants Paths |
IDH2 mutant IDH2 R172X |
Transcript | NM_002168.4 |
gDNA | chr15:g.90088605_90088607 |
cDNA | c.514_516 |
Protein | p.R172 |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002168.4 | chr15:g.90088605_90088607 | c.514_516 | p.R172 | RefSeq | GRCh38/hg38 |
NM_002168 | chr15:g.90088605_90088607 | c.514_516 | p.R172 | RefSeq | GRCh38/hg38 |
NM_002168.3 | chr15:g.90088605_90088607 | c.514_516 | p.R172 | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH2 R172X | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | IDH2 R172X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
IDH2 R172X | myelodysplastic syndrome | predicted - sensitive | Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) treatment was well tolerated and resulted in an overall response rate of 43% (9/21, 5 complete remission (CR), 1 partial remission, 1 marrow CR, 2 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were refractory to or progressed on hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
IDH2 R172X | oligodendroglioma | sensitive | Vorasidenib | FDA approved | Actionable | In a Phase III trial l (INDIGO) that supported FDA approval, Voranigo (vorasidenib) treatment significantly improved progression-free survival (27.7 vs 11.1 months, HR 0.39, p<0.001) and time to next intervention (HR 0.26, p<0.001) compared to placebo in adult and pediatric patients 12 years and older with WHO grade 2 oligodendroglioma or astrocytoma harboring susceptible IDH1 or IDH2 mutations, including IDH2 R172K/M/W/S/G (PMID: 37272516; NCT04164901). | detail... 37272516 |
IDH2 R172X | astrocytoma, IDH-mutant, grade 2 | sensitive | Vorasidenib | FDA approved | Actionable | In a Phase III trial l (INDIGO) that supported FDA approval, Voranigo (vorasidenib) treatment significantly improved progression-free survival (27.7 vs 11.1 months, HR 0.39, p<0.001) and time to next intervention (HR 0.26, p<0.001) compared to placebo in adult and pediatric patients 12 years and older with WHO grade 2 astrocytoma or oligodendroglioma harboring susceptible IDH1 or IDH2 mutations, including IDH2 R172K/M/W/S/G (PMID: 37272516; NCT04164901). | detail... 37272516 |
IDH2 R172X | myelodysplastic syndrome | predicted - sensitive | Azacitidine + Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) and Vidaza (azacitidine) combination treatment was well tolerated and resulted in an overall response rate of 68% (30/46, 11 complete remission (CR), 3 partial remission, 12 marrow CR, 4 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were naive to hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
IDH2 R172X | acute myeloid leukemia | predicted - sensitive | LY3410738 | Phase I | Actionable | In a Phase I trial, LY3410738 demonstrated safety and inhibited D-2-HG in patients with relapsed or refractory IDH-mutant acute myeloid leukemia, resulting in a composite complete remission (CRc) rate of 46% (6/13, 4 CR, 1 CRh, 1 CRi/CRp) in IDH inhibitor-naive patients harbor IDH2 R172 mutations (Cancer Res (2023) 83 (8_Supplement): CT026; NCT04603001). | detail... |