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Gene FLT3
Variant A848P
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions FLT3 A848P lies within the protein kinase domain of the Flt3 protein (UniProt.org). A848P results in growth factor independent cell proliferation, Flt3 phosphorylation, and Erk activation in culture (Blood; 2009, 114;22, Abstract #3982), and has been demonstrated to confer resistance to FLT3 inhibitors in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations in culture (PMID: 20520641), and therefore, is predicted to lead to a gain of Flt3 protein function.
Associated Drug Resistance Y
Category Variants Paths

FLT3 mutant FLT3 act mut FLT3 A848P

FLT3 mutant FLT3 exon21 FLT3 A848P

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Transcript NM_004119.3
gDNA chr13:g.28015701C>G
cDNA c.2542G>C
Protein p.A848P
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119 chr13:g.28015701C>G c.2542G>C p.A848P RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28015701C>G c.2542G>C p.A848P RefSeq GRCh38/hg38
NM_004119.2 chr13:g.28015701C>G c.2542G>C p.A848P RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P were resistant to Sutent (sunitinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor decreased response Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P acute myeloid leukemia predicted - sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and FLT3 A848P demonstrated sensitivity to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 A848P hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 ITD with FLT3 A848P in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 A848P hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3-ITD with FLT3 A848P were resistant to Nexavar (sorafenib) in culture (PMID: 20520641). 20520641
FLT3 exon 14 ins FLT3 A848P hematologic cancer resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3-ITD with FLT3 A848P were resistant to Sutent (sunitinib) in culture (PMID: 20520641). 20520641
FLT3 exon 14 ins FLT3 A848P hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of cells expressing FLT3-ITD with FLT3 A848P in culture (PMID: 20520641). 20520641
FLT3 exon 14 ins FLT3 A848P chronic myelomonocytic leukemia predicted - resistant Sorafenib + Sunitinib Case Reports/Case Series Actionable In a clinical case study, FLT3 A848P was identified after progression on the alternating treatment of Nexvar (sorafenib) and Sutent (sunitinib) in a patient with chronic myelomoncytic leukemia harboring a FLT3-ITD mutation (PMID: 20520641). 20520641