Annotation Detail
Information
- Associated Genes
- FLT3
- Associated Variants
-
FLT3 p.Asp835Tyr (p.D835Y)
(
ENST00000241453.12 )
FLT3 p.Asp835Tyr (p.D835Y) ( ENST00000241453.12 ) - Associated Disease
- acute myeloid leukemia
- Source Database
- CIViC Evidence
- Description
- An in-vitro saturation mutagenesis screen of 50 independently derived FLT3-ITD clones was performed to identify mutations that confer resistance to ponatinib. Mutations at 3 AL residues (D835 [n = 31], D839 [n = 3], and Y842 [n = 16]), with varying degrees of resistance to ponatinib were identified. FLT3 D835 mutations were shown to confer resistance to the tyrosine kinase inhibitor AC220 and ponatinib. This was especially found for D835Y and D835V mutations, whereas D835H mutations were found to confer moderate resistance to ponatinib but relatively minimal resistance to AC220.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1036
- Gene URL
- https://civic.genome.wustl.edu/links/genes/24
- Variant URL
- https://civic.genome.wustl.edu/links/variants/437
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Acute Myeloid Leukemia
- Evidence Direction
- Supports
- Drug
- Quizartinib,Ponatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 23430109
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Ponatinib | Resitance or Non-Reponse | true |
| Quizartinib | Resitance or Non-Reponse | true |