Gene Variant Detail

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Gene ATR
Variant F676fs
Impact List frameshift
Protein Effect loss of function - predicted
Gene Variant Descriptions ATR F676fs results in a change in the amino acid sequence of the Atr protein beginning at aa 676 of 2644, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the PI3K/PI4K domain and the FATC domain (UniProt.org), F676fs is predicted to lead to a loss of Atr protein function.
Associated Drug Resistance
Category Variants Paths

ATR mutant ATR inact mut ATR F676fs

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Transcript NM_001184.4
gDNA chr3:g.(142556435_142556436)
cDNA c.(2026_2025)
Protein p.F676fs
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001184.3 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
NM_001184 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
NM_001184.4 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_047448364.1 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_011512926 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_011512924.2 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_011512924 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_011512924.1 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_047448361.1 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_047448363.1 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_047448362.1 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38
XM_047448360.1 chr3:g.(142556435_142556436) c.(2026_2025) p.F676fs RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ATR inact mut prostate cancer sensitive Enzalutamide + Talazoparib Guideline Actionable Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic ATR mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). detail...
ATR inact mut prostate cancer sensitive Enzalutamide + Talazoparib FDA approved Actionable In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including ATR, with an HR of 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). detail... 37285865