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Gene | FLT3 |
Variant | M664I |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | FLT3 M664I lies within the protein kinase domain of the Flt3 protein (UniProt.org). M664I has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2023). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 exon16 FLT3 M664I |
Transcript | NM_004119.3 |
gDNA | chr13:g.28028239C>G |
cDNA | c.1992G>C |
Protein | p.M664I |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119.2 | chr13:g.28028239C>G | c.1992G>C | p.M664I | RefSeq | GRCh38/hg38 |
NM_004119 | chr13:g.28028239C>G | c.1992G>C | p.M664I | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28028239C>G | c.1992G>C | p.M664I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 M664I | Advanced Solid Tumor | decreased response | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 M664I displayed reduced sensitivity to PLX3397 relative to cells expressing FLT3-ITD in culture (PMID: 25847190). | 25847190 |
FLT3 exon 14 ins FLT3 M664I | 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 M664I in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 M664I | 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 M664I in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 M664I FLT3 F691L | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/M664I mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |