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    1. karim2001khoury 19 Feb 2026
      EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and

      [Paper-level Aggregated] PMCID: PMC8700411

      Evidence Type(s): Oncogenic, Predictive, Prognostic

      Justification: Oncogenic: The text describes EGFR exon 20 insertion mutations, including G770 equivalence, as being associated with sensitivity to specific EGFR TKIs, indicating their role in driving cancer progression. Predictive: The evidence suggests that patients with EGFR exon 20 insertion mutations, particularly those with G770 equivalence, can be predicted to respond to certain EGFR TKIs, such as afatinib and dacomitinib, based on preclinical and clinical data. Prognostic: The clinical outcomes reported for patients with EGFR exon 20 insertion mutations indicate that these mutations can influence treatment responses and outcomes, suggesting a prognostic role in advanced lung cancers.

      Gene→Variant (gene-first): EGFR(1956):D770 EGFR(1956):G770 EGFR(1956):Y764insFQEA EGFR(1956):D770_N771insSVD EGFR(1956):V769dupASV

      Genes: EGFR(1956)

      Variants: D770 G770 Y764insFQEA D770_N771insSVD V769dupASV

      CIViC paper-level aggregated PMC8700411
    2. karim2001khoury 19 Feb 2026
      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for a tenth of all EGFR mutations in lung cancers. An important unmet clinical need is the identification of EGFR exon 20 insertion mutants that

      [Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Diagnostic, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

      Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

      Genes: 1956

      Variants: D770 G770 Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Diagnostic Oncogenic
    3. karim2001khoury 19 Feb 2026
      Although these cases are limited in number and by reporting biases, they provide supporting evidence that EGFR-D770>GY and other exon 20 insertion mutations with G770 equivalence are sensitive to the clinically available

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive

      Justification: Predictive: The passage indicates that the variant G770 and other exon 20 insertion mutations are sensitive to specific EGFR TKIs, suggesting a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    4. karim2001khoury 19 Feb 2026
      The majority:but not all:of cases that received poziotinib or mobocertinib in this compiled cohort of advanced lung cancers harboring EGFR exon 20 insertion mutations with G770 equivalence had radiographic responses (Tab

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Diagnostic

      Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Diagnostic
    5. karim2001khoury 19 Feb 2026
      We identified seven reports from the literature and added one case from our institutional cohort that detailed partial clinical-radiographic parameters in patients with metastatic lung cancers harboring EGFR exon 20 inse

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of patients with metastatic lung cancers harboring EGFR exon 20 insertion mutations, including G770, to various EGFR TKIs, indicating a correlation with treatment response. Oncogenic: The mention of tumors harboring EGFR exon 20 insertion mutations, including G770, suggests that this somatic variant contributes to tumor development or progression in the context of metastatic lung cancers.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    6. karim2001khoury 19 Feb 2026
      3.3. Clinical Outcomes of Reported Patients with Advanced Lung Cancers Harboring EGFR Exon 20 Insertion Mutations Encompassing G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses patients with advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the variant is used to classify or define a specific disease subtype. Oncogenic: The mention of advanced lung cancers suggests that the G770 variant contributes to tumor development or progression, aligning with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    7. karim2001khoury 19 Feb 2026
      Our aforementioned preclinical results confirmed the structural modeling of EGFR-D770>GY (Figure 1A) and led us to speculate that patients with advanced lung cancers harboring EGFR exon 20 insertion mutations with a G770

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the potential response of patients with advanced lung cancers harboring the G770 variant to specific therapies, indicating a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    8. karim2001khoury 19 Feb 2026
      The exquisite sensitivity to 2nd generation EGFR TKIs was confirmed at the biochemical level. In Western blot experiments, the phosphorylated form of EGFR was readily inhibited by 10 nM and higher doses of dacomitinib in

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the sensitivity of the V769dupASV variant to 2nd generation EGFR TKIs, indicating a correlation with response to therapy. Functional: The variant V769dupASV is shown to alter the biochemical function of EGFR, as evidenced by the differing levels of inhibition of phosphorylated EGFR in response to dacomitinib.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Functional
    9. karim2001khoury 19 Feb 2026
      To highlight the differences in proliferation assays between Ba/F3 cells driven by the EGFR-D770>GY mutant and the more typical EGFR-A767_V769dupASV mutant, we show the dose-response curve for increasing concentrations o

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of cells with the A767_V769dupASV mutant to specific therapies (afatinib and dacomitinib), indicating a correlation between the variant and treatment sensitivity. Oncogenic: The variant A767_V769dupASV is mentioned in the context of proliferation assays, suggesting that it contributes to tumor development or progression in the tested cell lines.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    10. karim2001khoury 19 Feb 2026
      Our group generated a Ba/F3 cell line driven by the EGFR-D770>GY mutant in order to compare its properties with our previously described isogenic Ba/F3 preclinical models of exon 20 insertion mutants (Figure 2). To evalu

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity and resistance of various EGFR mutations, including D770_N771insSVD, V769dupASV, and Y764insFQEA, to different EGFR TKIs, indicating a correlation with response to therapy. Oncogenic: The variants mentioned are associated with the development of cancer, as they are described in the context of a Ba/F3 cell line model driven by specific EGFR mutations, which contribute to tumor behavior.

      Gene→Variant (gene-first): 1956:D770_N771insSVD 1956:V769dupASV 1956:Y764insFQEA

      Genes: 1956

      Variants: D770_N771insSVD V769dupASV Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    12. karim2001khoury 19 Feb 2026
      We queried three separate cohorts of EGFR exon 20 insertion mutations. Out of the 429 cases reported, 17 (3.96%) had the EGFR mutation leading to G770 equivalent change in the context of an insertion (Figure 1B). The typ

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses the prevalence of the G770 variant in a cohort of cases with EGFR exon 20 insertion mutations, indicating its association with a specific mutation type and providing context for its classification. Oncogenic: The mention of the G770 variant in the context of EGFR mutations suggests its role in tumor development or progression, as it is part of a known oncogenic pathway associated with cancer.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    13. karim2001khoury 19 Feb 2026
      3.1. Frequency of EGFR Exon 20 Insertions with a G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Diagnostic

      Justification: Diagnostic: The mention of "frequency" in relation to "EGFR Exon 20 Insertions with a G770 Equivalence" suggests that the variant is being used to classify or define a specific disease or subtype.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic
    14. karim2001khoury 19 Feb 2026
      Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for a tenth of all EGFR mutations in lung cancers. An important unmet clinical need is the identification of EGFR exon 20 insertion mutants that

      [Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Diagnostic, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

      Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

      Genes: 1956

      Variants: D770 G770 Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Diagnostic Oncogenic
    15. karim2001khoury 19 Feb 2026
      Although these cases are limited in number and by reporting biases, they provide supporting evidence that EGFR-D770>GY and other exon 20 insertion mutations with G770 equivalence are sensitive to the clinically available

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 13

      Evidence Type(s): Predictive

      Justification: Predictive: The passage indicates that the variant G770 and other exon 20 insertion mutations are sensitive to specific EGFR TKIs, suggesting a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    16. karim2001khoury 19 Feb 2026
      The majority:but not all:of cases that received poziotinib or mobocertinib in this compiled cohort of advanced lung cancers harboring EGFR exon 20 insertion mutations with G770 equivalence had radiographic responses (Tab

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

      Evidence Type(s): Predictive, Diagnostic

      Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Diagnostic
    17. karim2001khoury 19 Feb 2026
      We identified seven reports from the literature and added one case from our institutional cohort that detailed partial clinical-radiographic parameters in patients with metastatic lung cancers harboring EGFR exon 20 inse

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 10

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of patients with metastatic lung cancers harboring EGFR exon 20 insertion mutations, including G770, to various EGFR TKIs, indicating a correlation with treatment response. Oncogenic: The mention of tumors harboring EGFR exon 20 insertion mutations, including G770, suggests that this somatic variant contributes to tumor development or progression in the context of metastatic lung cancers.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    18. karim2001khoury 19 Feb 2026
      3.3. Clinical Outcomes of Reported Patients with Advanced Lung Cancers Harboring EGFR Exon 20 Insertion Mutations Encompassing G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses patients with advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the variant is used to classify or define a specific disease subtype. Oncogenic: The mention of advanced lung cancers suggests that the G770 variant contributes to tumor development or progression, aligning with the definition of an oncogenic variant.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    19. karim2001khoury 19 Feb 2026
      Our aforementioned preclinical results confirmed the structural modeling of EGFR-D770>GY (Figure 1A) and led us to speculate that patients with advanced lung cancers harboring EGFR exon 20 insertion mutations with a G770

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 8

      Evidence Type(s): Predictive

      Justification: Predictive: The passage discusses the potential response of patients with advanced lung cancers harboring the G770 variant to specific therapies, indicating a correlation with treatment response.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Predictive
    20. karim2001khoury 19 Feb 2026
      The exquisite sensitivity to 2nd generation EGFR TKIs was confirmed at the biochemical level. In Western blot experiments, the phosphorylated form of EGFR was readily inhibited by 10 nM and higher doses of dacomitinib in

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 7

      Evidence Type(s): Predictive, Functional

      Justification: Predictive: The passage discusses the sensitivity of the V769dupASV variant to 2nd generation EGFR TKIs, indicating a correlation with response to therapy. Functional: The variant V769dupASV is shown to alter the biochemical function of EGFR, as evidenced by the differing levels of inhibition of phosphorylated EGFR in response to dacomitinib.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Functional
    21. karim2001khoury 19 Feb 2026
      To highlight the differences in proliferation assays between Ba/F3 cells driven by the EGFR-D770>GY mutant and the more typical EGFR-A767_V769dupASV mutant, we show the dose-response curve for increasing concentrations o

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 6

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the response of cells with the A767_V769dupASV mutant to specific therapies (afatinib and dacomitinib), indicating a correlation between the variant and treatment sensitivity. Oncogenic: The variant A767_V769dupASV is mentioned in the context of proliferation assays, suggesting that it contributes to tumor development or progression in the tested cell lines.

      Gene→Variant (gene-first): 1956:V769dupASV

      Genes: 1956

      Variants: V769dupASV

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    22. karim2001khoury 19 Feb 2026
      Our group generated a Ba/F3 cell line driven by the EGFR-D770>GY mutant in order to compare its properties with our previously described isogenic Ba/F3 preclinical models of exon 20 insertion mutants (Figure 2). To evalu

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 5

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The passage discusses the sensitivity and resistance of various EGFR mutations, including D770_N771insSVD, V769dupASV, and Y764insFQEA, to different EGFR TKIs, indicating a correlation with response to therapy. Oncogenic: The variants mentioned are associated with the development of cancer, as they are described in the context of a Ba/F3 cell line model driven by specific EGFR mutations, which contribute to tumor behavior.

      Gene→Variant (gene-first): 1956:D770_N771insSVD 1956:V769dupASV 1956:Y764insFQEA

      Genes: 1956

      Variants: D770_N771insSVD V769dupASV Y764insFQEA

      CIViC paragraph-level PMC8700411 Predictive Oncogenic
    24. karim2001khoury 19 Feb 2026
      We queried three separate cohorts of EGFR exon 20 insertion mutations. Out of the 429 cases reported, 17 (3.96%) had the EGFR mutation leading to G770 equivalent change in the context of an insertion (Figure 1B). The typ

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

      Evidence Type(s): Diagnostic, Oncogenic

      Justification: Diagnostic: The passage discusses the prevalence of the G770 variant in a cohort of cases with EGFR exon 20 insertion mutations, indicating its association with a specific mutation type and providing context for its classification. Oncogenic: The mention of the G770 variant in the context of EGFR mutations suggests its role in tumor development or progression, as it is part of a known oncogenic pathway associated with cancer.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic Oncogenic
    25. karim2001khoury 19 Feb 2026
      3.1. Frequency of EGFR Exon 20 Insertions with a G770 Equivalence

      [Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

      Evidence Type(s): Diagnostic

      Justification: Diagnostic: The mention of "frequency" in relation to "EGFR Exon 20 Insertions with a G770 Equivalence" suggests that the variant is being used to classify or define a specific disease or subtype.

      Gene→Variant (gene-first): 1956:G770

      Genes: 1956

      Variants: G770

      CIViC paragraph-level PMC8700411 Diagnostic
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    pmc.ncbi.nlm.nih.gov/articles/PMC8700411/pdf/cells-10-03561.pdf