[Paper-level Aggregated] PMCID: PMC2970593

Evidence Type(s): Functional

Summary: Mutation: W731 | Summary: The W731 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: E734 | Summary: The E734 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: T785 | Summary: The T785 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: C797 | Summary: The C797 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: Y801 | Summary: The Y801 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: R831 | Summary: The R831 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: L858 | Summary: The L858 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: E868 | Summary: The E868 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Evidence Type: Functional Mutation: L858R | Summary: The L858R mutation is described as a functional mutation that is activating in nature.

Gene→Variant (gene-first): NA:W731 NA:E734 NA:T785 EGFR(1956):C797 EGFR(1956):Y801 EGFR(1956):R831 EGFR(1956):L858 EGFR(1956):E868 EGFR(1956):L858R

Genes: NA EGFR(1956)

Variants: W731 E734 T785 C797 Y801 R831 L858 E868 L858R

[Paper-level Aggregated] PMCID: PMC2970593

Evidence Type(s): Oncogenic

Summary: Mutation: C797Y | Summary: The C797Y mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Evidence Type: Oncogenic Mutation: E734Q | Summary: The E734Q mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Evidence Type: Oncogenic Mutation: E868G | Summary: The E868G mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Evidence Type: Oncogenic Mutation: L831H | Summary: The L831H mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development and increasing sensitivity to the EGFR inhibitor Erlotinib.

Evidence Type: Oncogenic Mutation: T785A | Summary: The T785A mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Evidence Type: Oncogenic Mutation: W731L | Summary: The W731L mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Evidence Type: Oncogenic Mutation: Y801H | Summary: The Y801H mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Gene→Variant (gene-first): EGFR(1956):C797Y EGFR(1956):E734Q EGFR(1956):E868G EGFR(1956):L831H EGFR(1956):L858R EGFR(1956):T785A EGFR(1956):W731L EGFR(1956):Y801H

Genes: EGFR(1956)

Variants: C797Y E734Q E868G L831H L858R T785A W731L Y801H

[Paper-level Aggregated] PMCID: PMC2970593

Evidence Type(s): Prognostic

Summary: Mutation: L858R | Summary: Patients with the L858R mutation had a median follow-up time of 22 months, with some developing progressive disease and death, suggesting a correlation with disease outcome.

Gene→Variant (gene-first): EGFR(1956):L858R

Genes: EGFR(1956)

Variants: L858R

[Paper-level Aggregated] PMCID: PMC2970593

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation is responsive to erlotinib, indicating a correlation with treatment response.

Evidence Type: Predictive

Gene→Variant (gene-first): EGFR(1956):L858R

Genes: EGFR(1956)

Variants: L858R

[Paragraph-level] PMCID: PMC2970593 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Functional, Predictive, Prognostic

Summary: Evidence Type: Functional | Mutation: L858R | Summary: The L858R mutation is described as a functional mutation that is activating in nature. Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation is responsive to erlotinib, indicating a correlation with treatment response. Evidence Type: Prognostic | Mutation: L858R | Summary: Patients with the L858R mutation had a median follow-up time of 22 months, with some developing progressive disease and death, suggesting a correlation with disease outcome.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: W731 | Summary: The W731 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: E734 | Summary: The E734 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: T785 | Summary: The T785 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: C797 | Summary: The C797 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: Y801 | Summary: The Y801 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: R831 | Summary: The R831 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: L858 | Summary: The L858 mutation alters molecular function as it is located in the TK domain critical for EGFR activity. Evidence Type: Functional | Mutation: E868 | Summary: The E868 mutation alters molecular function as it is located in the TK domain critical for EGFR activity.

Gene→Variant (gene-first): 1956:C797 NA:E734 NA:T785 1956:E868 1956:L858 1956:R831 NA:W731 1956:Y801

Genes: 1956 NA

Variants: C797 E734 T785 E868 L858 R831 W731 Y801

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C797Y | Summary: The C797Y mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: E734Q | Summary: The E734Q mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: E868G | Summary: The E868G mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: L831H | Summary: The L831H mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development and increasing sensitivity to the EGFR inhibitor Erlotinib. Evidence Type: Oncogenic | Mutation: T785A | Summary: The T785A mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: W731L | Summary: The W731L mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development. Evidence Type: Oncogenic | Mutation: Y801H | Summary: The Y801H mutation is identified as a somatic variant in the tyrosine kinase domain of EGFR, contributing to tumor development.

Gene→Variant (gene-first): 1956:C797Y 1956:E734Q 1956:E868G 1956:L831H 1956:L858R 1956:T785A 1956:W731L 1956:Y801H

Genes: 1956

Variants: C797Y E734Q E868G L831H L858R T785A W731L Y801H

[Paper-level Aggregated] PMCID: PMC2970593

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The mutations identified in the EGFR tyrosine kinase domain, including L858R, are described as activating mutations that increase sensitivity to the EGFR inhibitor Erlotinib, indicating their role in promoting cancer progression. Predictive: The presence of the L858R mutation is associated with increased sensitivity to the EGFR inhibitor Erlotinib, suggesting its utility in predicting response to targeted therapy in patients with non-small cell lung cancer. Functional: The text states that all missense mutations, including the novel ones, were found to be activating mutations, indicating their functional impact on EGFR activity.

Gene→Variant (gene-first): EGFR(1956):C797 NA:E734 NA:T785 EGFR(1956):E868 EGFR(1956):L858 EGFR(1956):R831 NA:W731 EGFR(1956):Y801 EGFR(1956):C797Y EGFR(1956):E734Q EGFR(1956):E868G EGFR(1956):L831H EGFR(1956):L858R EGFR(1956):T785A EGFR(1956):W731L EGFR(1956):Y801H

Genes: EGFR(1956) NA

Variants: C797 E734 T785 E868 L858 R831 W731 Y801 C797Y E734Q E868G L831H L858R T785A W731L Y801H

[Paragraph-level] PMCID: PMC2970593 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage indicates that the L858R mutation is an activating mutation that is responsive to erlotinib, suggesting a correlation with treatment response. Oncogenic: The mention of the L858R mutation as an activating mutation implies its contribution to tumor development or progression, consistent with oncogenic behavior.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses mutations in the TK domain of EGFR that are critical for its activity, indicating that these variants alter molecular function related to protein activity. Oncogenic: The context of the mutations being in the TK domain of EGFR suggests that they may contribute to tumor development or progression, as this domain is often implicated in oncogenic signaling pathways.

Gene→Variant (gene-first): 1956:C797 NA:E734 NA:T785 1956:E868 1956:L858 1956:R831 NA:W731 1956:Y801

Genes: 1956 NA

Variants: C797 E734 T785 E868 L858 R831 W731 Y801

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage states that the L858R mutation was found to increase sensitivity to the EGFR inhibitor, Erlotinib, indicating a correlation with treatment response. Oncogenic: All mutations mentioned in the passage, including C797Y, E734Q, E868G, L831H, L858R, T785A, W731L, and Y801H, are described as somatic mutations that contribute to tumor development, as they were identified in the tyrosine kinase domain of EGFR in cancer samples.

Gene→Variant (gene-first): 1956:C797Y 1956:E734Q 1956:E868G 1956:L831H 1956:L858R 1956:T785A 1956:W731L 1956:Y801H

Genes: 1956

Variants: C797Y E734Q E868G L831H L858R T785A W731L Y801H

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses mutations in the TK domain of EGFR that are critical for its activity, indicating that these variants alter molecular function related to protein activity. Oncogenic: The context of the mutations being in the TK domain of EGFR suggests that they may contribute to tumor development or progression, as this domain is often implicated in oncogenic signaling pathways.

Gene→Variant (gene-first): 1956:C797 NA:E734 NA:T785 1956:E868 1956:L858 1956:R831 NA:W731 1956:Y801

Genes: 1956 NA

Variants: C797 E734 T785 E868 L858 R831 W731 Y801

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage states that the L858R mutation was found to increase sensitivity to the EGFR inhibitor, Erlotinib, indicating a correlation with treatment response. Oncogenic: All mutations mentioned in the passage, including C797Y, E734Q, E868G, L831H, L858R, T785A, W731L, and Y801H, are described as somatic mutations that contribute to tumor development, as they were identified in the tyrosine kinase domain of EGFR in cancer samples.

Gene→Variant (gene-first): 1956:C797Y 1956:E734Q 1956:E868G 1956:L831H 1956:L858R 1956:T785A 1956:W731L 1956:Y801H

Genes: 1956

Variants: C797Y E734Q E868G L831H L858R T785A W731L Y801H