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Gene FLT3
Variant D835I
Impact List missense
Protein Effect unknown
Gene Variant Descriptions FLT3 D835I lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835I has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 27908881), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Dec 2023).
Associated Drug Resistance Y
Category Variants Paths

FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835I

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Transcript NM_004119.3
gDNA chr13:g.28018504_28018505delGAinsAT
cDNA c.2503_2504delGAinsAT
Protein p.D835I
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119 chr13:g.28018504_28018505delTCinsAT c.2503_2504delGAinsAT p.D835I RefSeq GRCh38/hg38
NM_004119.2 chr13:g.28018504_28018505delGAinsAT c.2503_2504delGAinsAT p.D835I RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018504_28018505delGAinsAT c.2503_2504delGAinsAT p.D835I 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 D835I hematologic cancer predicted - sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835I demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - resistant Quizartinib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835I was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Vanflyta (quizartinib) after an initial response (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability and inhibition of Flt3 phosphorylation (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I 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 D835I in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835I were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Crenolanib Case Reports/Case Series Actionable In a clinical case study, FLT3 F691L was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I whose disease progressed following Crenolanib (CP-868596) treatment (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Crenolanib (CP-868596) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Xospata (gilteritinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Vanflyta (quizartinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). 27908881