Annotation Detail
Information
- Associated Genes
- BTK
- Associated Variants
-
BTK p.Thr350Ala (p.T350A)
(
ENST00000308731.8,
ENST00000621635.4,
ENST00000695614.1,
ENST00000695615.1,
ENST00000695617.1,
ENST00000695622.1,
ENST00000695623.1,
ENST00000695625.1,
ENST00000703407.1 )
BTK p.Thr350Ala (p.T350A) ( ENST00000308731.8, ENST00000621635.4, ENST00000695614.1, ENST00000695615.1, ENST00000695617.1, ENST00000695622.1, ENST00000695623.1, ENST00000695625.1, ENST00000703407.1 ) - Associated Disease
- chronic lymphocytic leukemia
- Source Database
- CIViC Evidence
- Description
- Case report of a patient with CLL and Richter-transformed relapse under ibrutinib (after an initial partial response for 10 months). Sequencing of sequential samples of this patient revealed a novel BTK T316 mutation at relapse (allele frequency of 75%). Characterization of this mutation showed that is was located on the SH2 domain, not associated with Ibrutinib binding. Introduction of this mutation in an Ibrutinib-sensitive lymphoma cell line showed resistance comparable to the known C481 resistance mutations, which was also confirmed by absence of downstream signaling.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1985
- Gene URL
- https://civic.genome.wustl.edu/links/genes/65
- Variant URL
- https://civic.genome.wustl.edu/links/variants/870
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Chronic Lymphocytic Leukemia
- Evidence Direction
- Supports
- Drug
- Ibrutinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 27626698
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Ibrutinib | Resitance or Non-Reponse | true |