Gene Variant Detail

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Gene BTK
Variant T474I
Impact List missense
Protein Effect no effect
Gene Variant Descriptions BTK T474I lies within the protein kinase domain of the Btk protein (UniProt.org). T474I demonstrates kinase activity similar to wild-type Btk in cultured cells (PMID: 27571029, PMID: 28573668, PMID: 33526860).
Associated Drug Resistance

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Transcript NM_000061.2
gDNA chrX:g.101356197G>A
cDNA c.1421C>T
Protein p.T474I
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000061 chrX:g.101356197G>A c.1421C>T p.T474I RefSeq GRCh38/hg38
NM_000061.2 chrX:g.101356197G>A c.1421C>T p.T474I RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BTK T474I diffuse large B-cell lymphoma sensitive Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, Imbruvica (ibrutinib) treatment inhibited phosphorylation of Btk and decreased viability of a diffuse large B-cell lymphoma cell line expressing BTK T474I in culture (PMID: 35196427). 35196427
BTK T474I Advanced Solid Tumor predicted - sensitive Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) resulted in reduced Btk activity in cell lines expressing BTK T474I in culture (PMID: 33526860). 33526860
BTK T474I chronic lymphocytic leukemia predicted - resistant LOXO-305 Case Reports/Case Series Actionable In a clinical case study, two patients with chronic lymphocytic leukemia who previously responded to LOXO-305 treatment were found to have acquired BTK T474I upon disease progression (PMID: 35196427). 35196427
BTK T474I diffuse large B-cell lymphoma resistant Vecabrutinib Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK T474I demonstrated resistance to Vecabrutinib (SNS-062) in culture (PMID: 35196427). 35196427
BTK T474I diffuse large B-cell lymphoma resistant Fenebrutinib Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK T474I demonstrated resistance to Fenebrutinib (GDC-0853) in culture (PMID: 35196427). 35196427
BTK T474I diffuse large B-cell lymphoma resistant LOXO-305 Preclinical - Cell culture Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK T474I demonstrated resistance to LOXO-305 in culture (PMID: 35196427). 35196427
BTK T474I BTK C481S Advanced Solid Tumor predicted - sensitive Fenebrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Fenebrutinib (GDC-0853) resulted in reduced Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - sensitive RN486 Preclinical - Biochemical Actionable In a preclinical study, treatment with RN486 resulted in reduced Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Zanubrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Brukinsa (zanubrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant CGI1746 Preclinical - Biochemical Actionable In a preclinical study, treatment with CGI1746 failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Ibrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Imbruvica (ibrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK C481S Advanced Solid Tumor predicted - resistant Acalabrutinib Preclinical - Biochemical Actionable In a preclinical study, treatment with Calquence (acalabrutinib) failed to inhibit Btk activity in a cell line expressing BTK variants T474I and C481S in culture (PMID: 33526860). 33526860
BTK T474I BTK L528W chronic lymphocytic leukemia predicted - resistant LOXO-305 Case Reports/Case Series Actionable In a clinical case study, a patient with chronic lymphocytic leukemia harboring BTK C481S who previously responded to LOXO-305 treatment was found to have acquired BTK T474I and BTK L528W upon disease progression (PMID: 35196427). 35196427
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References