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Gene | IDH2 |
Variant | R172W |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | IDH2 R172W lies within the active site of the Idh2 protein (PMID: 19228619). R172W is associated with increased 2-hydroxyglutarate (2-HG) levels in patient samples (PMID: 34829476, PMID: 22180306), and therefore, is predicted to lead to a gain of Idh2 protein function. |
Associated Drug Resistance | |
Category Variants Paths |
IDH2 mutant IDH2 act mut IDH2 R172W IDH2 mutant IDH2 R172X IDH2 R172W |
Transcript | NM_002168.4 |
gDNA | chr15:g.90088607T>A |
cDNA | c.514A>T |
Protein | p.R172W |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002168.3 | chr15:g.90088607T>A | c.514A>T | p.R172W | RefSeq | GRCh38/hg38 |
NM_002168 | chr15:g.90088607T>A | c.514A>T | p.R172W | RefSeq | GRCh38/hg38 |
NM_002168.4 | chr15:g.90088607T>A | c.514A>T | p.R172W | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH2 R172W | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172W is on the companion diagnostic. | 28588020 detail... detail... |
IDH2 R172W | acute myeloid leukemia | predicted - sensitive | Enasidenib + Venetoclax | Case Reports/Case Series | Actionable | In a Phase Ib/II trial, Idhifa (enasidenib) plus Venclexta (venetoclax) was well tolerated and demonstrated activity in relapsed or refractory acute myeloid leukemia patients harboring IDH2 R140Q (15/27) or IDH2 R172K/W (12/27), with an overall response rate (ORR) of 70% (16/23), with complete remission (CR) in 57% (13/23) of evaluable patients, and an ORR of 83% (10/12) and a CR rate of 67% (8/12) in patients harboring IDH2 R172K or IDH2 R172W (Blood (2023) 142 (Supplement 1): 159; NCT04092179). | detail... |