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Gene | FLT3 |
Variant | F691I |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | FLT3 F691I lies within the protein kinase domain of the Flt3 protein (PMID: 23430109). F691I has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 23392356, PMID: 22409268), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2024). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 exon17 FLT3 F691I |
Transcript | NM_004119.3 |
gDNA | chr13:g.28027224A>T |
cDNA | c.2071T>A |
Protein | p.F691I |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011535015 | chr13:g.28027167A>T | c.2071T>A | p.F691I | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28027224A>T | c.2071T>A | p.F691I | RefSeq | GRCh38/hg38 |
NM_004119 | chr13:g.28027224A>T | c.2071T>A | p.F691I | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28027224A>T | c.2071T>A | p.F691I | RefSeq | GRCh38/hg38 |
XM_011535015.3 | chr13:g.28027167A>T | c.2071T>A | p.F691I | RefSeq | GRCh38/hg38 |
XM_011535015.2 | chr13:g.28027167A>T | c.2071T>A | p.F691I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | decreased response | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a FLT3-ITD mutation and FLT3 F691I demonstrated reduced sensitivity to Alunbrig (brigatinib) compared to cells expressing FLT3-ITD alone in culture (PMID: 27780853). | 27780853 |
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I demonstrated reduced response to Sutent (sunitinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 F691I | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 phosphorylation and inhibited growth of transformed cells expressing FLT3-ITD and FLT3 F691I in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). | 32247263 |