[Paper-level Aggregated] PMCID: PMC1702556

Evidence Type(s): Functional

Summary: Mutation: A289V | Summary: The A289V mutation in EGFR shows a marked increase in receptor autophosphorylation and is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells, indicating an alteration in molecular function.

Evidence Type: Functional Mutation: T263P | Summary: The T263P mutation in EGFR is part of a panel of missense mutants that exhibit increased phosphotyrosine content and is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells, suggesting a change in biochemical function.

Evidence Type: Functional Mutation: G598V | Summary: The G598V mutation is included in a panel of EGFR missense mutants that demonstrate increased phosphotyrosine content and is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells, indicating a functional alteration.

Evidence Type: Functional Mutation: L861Q | Summary: The L861Q mutation is part of a group of EGFR missense mutants that show increased phosphotyrosine content and is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells, reflecting a change in molecular function.

Evidence Type: Functional Mutation: R108K | Summary: The R108K mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells.

Gene→Variant (gene-first): EGFR(1956):A289V EGFR(1956):T263P EGFR(1956):G598V EGFR(1956):L861Q EGFR(1956):R108K

Genes: EGFR(1956)

Variants: A289V T263P G598V L861Q R108K

[Paper-level Aggregated] PMCID: PMC1702556

Evidence Type(s): Oncogenic

Summary: Mutation: L861Q | Summary: The L861Q mutation in the EGFR kinase domain is identified as a missense mutation in glioblastoma, contributing to tumor development and oncogenesis, as evidenced by its role in anchorage-independent colony formation in NIH-3T3 cells and tumor formation in mice.

Evidence Type: Oncogenic Mutation: A289 | Summary: The A289 mutation is noted as one of the evolutionarily conserved residues affected by mutations in glioblastomas, suggesting its contribution to tumor progression. The A289D and A289T variants are found in tumors without matched normal tissue, indicating their potential roles in tumor development. Additionally, the A289V mutation demonstrates oncogenic properties by facilitating anchorage-independent colony formation in NIH-3T3 cells and is associated with tumor development in mice.

Evidence Type: Oncogenic Mutation: R108 | Summary: The R108 mutation is identified as an evolutionarily conserved residue affected by mutations in glioblastomas, indicating its potential role in tumor development. The R108K variant contributes to tumor development, allowing for anchorage-independent colony formation in NIH-3T3 cells and leading to large tumors in mice expressing this mutant.

Evidence Type: Oncogenic Mutation: E330K | Summary: The E330K mutation is described as germline but is also noted in the context of tumor samples, suggesting its involvement in oncogenic processes.

Evidence Type: Oncogenic Mutation: R324L | Summary: The R324L mutation is noted in tumors without matched normal tissue, indicating its potential role in tumor development.

Evidence Type: Oncogenic Mutation: T263P | Summary: The T263P mutation in EGFR is associated with oncogenic behavior, enabling anchorage-independent colony formation in NIH-3T3 cells and leading to tumor formation in mice.

Evidence Type: Oncogenic Mutation: G598V | Summary: The G598V mutation in EGFR is implicated in oncogenic activity, supporting anchorage-independent colony formation in NIH-3T3 cells and contributing to tumor progression, as evidenced by significant tumors produced in the animal model.

Evidence Type: Oncogenic Mutation: L858R | Summary: The L858R mutation is suggested to play a role in gliomagenesis and contributes to tumor development, as indicated by its oncogenicity in transformation assays.

Gene→Variant (gene-first): EGFR(1956):L861Q EGFR(1956):A289 EGFR(1956):R108 EGFR(1956):E330K EGFR(1956):R324L EGFR(1956):T263P EGFR(1956):G598V EGFR(1956):L858R

Genes: EGFR(1956)

Variants: L861Q A289 R108 E330K R324L T263P G598V L858R

[Paper-level Aggregated] PMCID: PMC1702556

Evidence Type(s): Diagnostic

Summary: Mutation: R108K | Summary: The R108K mutation is associated with defining the presence of EGFR missense mutations in gliomas, indicating its role in classifying the disease.

Evidence Type: Diagnostic Mutation: T263P | Summary: The T263P mutation is part of the common amino acid changes in EGFR missense mutations, contributing to the classification of gliomas.

Evidence Type: Diagnostic Mutation: A289V | Summary: The A289V mutation is identified as one of the common amino acid changes in EGFR missense mutations, aiding in the diagnosis of gliomas.

Evidence Type: Diagnostic Mutation: G598V | Summary: The G598V mutation is included among the common amino acid changes in EGFR missense mutations, which helps in the diagnostic classification of gliomas.

Gene→Variant (gene-first): EGFR(1956):R108K EGFR(1956):T263P EGFR(1956):A289V EGFR(1956):G598V

Genes: EGFR(1956)

Variants: R108K T263P A289V G598V

[Paper-level Aggregated] PMCID: PMC1702556

Evidence Type(s): Predictive

Summary: Mutation: L858R | Summary: The L858R mutation may sensitize transformed cells to EGFR kinase inhibitors, indicating a correlation with response to therapy.

Evidence Type: Predictive Mutation: L861Q | Summary: The L861Q mutation is suggested to sensitize transformed cells to EGFR kinase inhibitors, indicating a potential response to therapy.

Evidence Type: Predictive Mutation: L790M | Summary: The L790M mutation, in combination with L858R, is described as drug-resistant, suggesting a role in therapy resistance to EGFR kinase inhibitors.

Evidence Type: Predictive Mutation: R108K | Summary: The R108K mutation in EGFR was associated with clinical responses to erlotinib in gliomas, suggesting a correlation with treatment sensitivity, and was also identified in gliomas that failed EGFR kinase inhibitor therapy, indicating a possible link to treatment resistance.

Gene→Variant (gene-first): EGFR(1956):L858R EGFR(1956):L861Q NA:L790M EGFR(1956):R108K

Genes: EGFR(1956) NA

Variants: L858R L861Q L790M R108K

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: R108K | Summary: The R108K mutation in EGFR was associated with clinical responses to erlotinib in gliomas, suggesting a correlation with treatment sensitivity. Evidence Type: Oncogenic | Mutation: R108K | Summary: The presence of the R108K mutation in gliomas indicates its potential role in tumor development or progression, particularly in the context of EGFR amplification. Evidence Type: Predictive | Mutation: R108K | Summary: The R108K mutation was also identified in gliomas that failed EGFR kinase inhibitor therapy, indicating a possible link to treatment resistance.

Gene→Variant (gene-first): 1956:R108K

Genes: 1956

Variants: R108K

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic, Predictive

Summary: Evidence Type: Oncogenic | Mutation: L858R | Summary: The L858R mutation is suggested to play a role in gliomagenesis and contributes to tumor development as indicated by its oncogenicity in transformation assays. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation is implicated in gliomagenesis and is associated with tumor development, as evidenced by its oncogenic behavior in standard transformation assays. Evidence Type: Predictive | Mutation: L858R | Summary: The L858R mutation may sensitize transformed cells to EGFR kinase inhibitors, indicating a correlation with response to therapy. Evidence Type: Predictive | Mutation: L861Q | Summary: The L861Q mutation is suggested to sensitize transformed cells to EGFR kinase inhibitors, indicating a potential response to therapy. Evidence Type: Predictive | Mutation: L790M | Summary: The L790M mutation, in combination with L858R, is described as drug-resistant, suggesting a role in therapy resistance to EGFR kinase inhibitors.

Gene→Variant (gene-first): 1956:L858R 1956:L861Q 1956:T790M

Genes: 1956

Variants: L858R L861Q T790M

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A289V | Summary: The A289V mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: G598V | Summary: The G598V mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: L861Q | Summary: The L861Q mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: R108K | Summary: The R108K mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells. Evidence Type: Functional | Mutation: T263P | Summary: The T263P mutation alters molecular function, as it is associated with increased tyrosine phosphorylation in response to EGF stimulation in murine hematopoietic cells.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: A289V | Summary: The A289V mutation in EGFR shows a marked increase in receptor autophosphorylation, indicating an alteration in molecular function. Evidence Type: Functional | Mutation: T263P | Summary: The T263P mutation in EGFR is part of a panel of missense mutants that exhibit increased phosphotyrosine content, suggesting a change in biochemical function. Evidence Type: Functional | Mutation: G598V | Summary: The G598V mutation is included in a panel of EGFR missense mutants that demonstrate increased phosphotyrosine content, indicating a functional alteration. Evidence Type: Functional | Mutation: L861Q | Summary: The L861Q mutation is part of a group of EGFR missense mutants that show increased phosphotyrosine content, reflecting a change in molecular function.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: R108K | Summary: The R108K mutation in EGFR was shown to contribute to tumor development, as NIH-3T3 cells expressing this mutant produced large tumors in mice. Evidence Type: Oncogenic | Mutation: T263P | Summary: The T263P mutation in EGFR demonstrated oncogenic potential, leading to tumor formation in NIH-3T3 cells inoculated in mice. Evidence Type: Oncogenic | Mutation: A289V | Summary: The A289V mutation in EGFR was associated with tumor development, as evidenced by large tumors formed in mice expressing this mutant. Evidence Type: Oncogenic | Mutation: G598V | Summary: The G598V mutation in EGFR contributed to tumor progression, as NIH-3T3 cells expressing this variant produced significant tumors in the animal model. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation in EGFR was implicated in oncogenesis, resulting in tumor formation in mice injected with NIH-3T3 cells expressing this mutant.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: R108K | Summary: The R108K mutation in EGFR contributes to tumor development as it allows for anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: T263P | Summary: The T263P mutation in EGFR is associated with oncogenic behavior, as it enables anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: A289V | Summary: The A289V mutation in EGFR demonstrates oncogenic properties by facilitating anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: G598V | Summary: The G598V mutation in EGFR is implicated in oncogenic activity, as it supports anchorage-independent colony formation in NIH-3T3 cells. Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation in EGFR is shown to have oncogenic potential, contributing to anchorage-independent colony formation in NIH-3T3 cells.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic

Summary: Evidence Type: Diagnostic | Mutation: R108K | Summary: The R108K mutation is associated with defining the presence of EGFR missense mutations in gliomas, indicating its role in classifying the disease. Evidence Type: Diagnostic | Mutation: T263P | Summary: The T263P mutation is part of the common amino acid changes in EGFR missense mutations, contributing to the classification of gliomas. Evidence Type: Diagnostic | Mutation: A289V | Summary: The A289V mutation is identified as one of the common amino acid changes in EGFR missense mutations, aiding in the diagnosis of gliomas. Evidence Type: Diagnostic | Mutation: G598V | Summary: The G598V mutation is included among the common amino acid changes in EGFR missense mutations, which helps in the diagnostic classification of gliomas.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: L861Q | Summary: The L861Q mutation in the EGFR kinase domain is identified as a missense mutation in glioblastoma, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: A289 | Summary: The A289 mutation is noted as one of the evolutionarily conserved residues affected by mutations in glioblastomas, suggesting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: R108 | Summary: The R108 mutation is also identified as an evolutionarily conserved residue affected by mutations in glioblastomas, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: E330K | Summary: The E330K mutation is described as germline, but it is also noted in the context of tumor samples, suggesting its involvement in oncogenic processes. Evidence Type: Oncogenic | Mutation: A289D | Summary: The A289D mutation is found in tumors without matched normal tissue, indicating its potential role in tumor development. Evidence Type: Oncogenic | Mutation: A289T | Summary: The A289T mutation is identified in tumors for which no normal tissue was available, suggesting its contribution to tumor progression. Evidence Type: Oncogenic | Mutation: R324L | Summary: The R324L mutation is noted in tumors without matched normal tissue, indicating its potential role in tumor development.

Gene→Variant (gene-first): 1956:A289 1956:A289D 1956:A289T 1956:E330K 1956:L861Q 1956:R108 1956:R324L

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L

[Paper-level Aggregated] PMCID: PMC1702556

Evidence Type(s): Oncogenic, Predictive, Diagnostic, Prognostic

Justification: Oncogenic: The presence of identical missense mutations in multiple patient samples and their oncogenicity in transformation assays suggest that these mutants play a role in gliomagenesis. Predictive: The data indicate that EGFR missense mutants sensitize transformed cells to EGFR kinase inhibitors, suggesting their potential as predictive biomarkers for response to therapy. Diagnostic: The identification of specific EGFR missense mutations in glioblastoma samples supports their use as diagnostic markers for this type of cancer. Prognostic: The association of certain EGFR mutations with clinical responses to EGFR kinase inhibitors implies that these mutations may have prognostic significance in glioblastoma treatment outcomes.

Gene→Variant (gene-first): EGFR(1956):A289 EGFR(1956):A289D EGFR(1956):A289T EGFR(1956):E330K EGFR(1956):L861Q EGFR(1956):R108 EGFR(1956):R324L EGFR(1956):A289V EGFR(1956):G598V EGFR(1956):R108K EGFR(1956):T263P EGFR(1956):L858R EGFR(1956):T790M

Genes: EGFR(1956)

Variants: A289 A289D A289T E330K L861Q R108 R324L A289V G598V R108K T263P L858R T790M

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the association of the R108K variant with clinical responses to EGFR kinase inhibitors, indicating a correlation with treatment response. Oncogenic: The R108K variant is identified in gliomas, suggesting its potential role in tumor development or progression, particularly in the context of EGFR amplification.

Gene→Variant (gene-first): 1956:R108K

Genes: 1956

Variants: R108K

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the presence of EGFR missense mutants, including L858R and L861Q, may sensitize transformed cells to EGFR kinase inhibitors, indicating a correlation with treatment response. Oncogenic: The identical missense mutations are described as having oncogenicity and playing a role in gliomagenesis, suggesting that these somatic variants contribute to tumor development.

Gene→Variant (gene-first): 1956:L858R 1956:L861Q 1956:T790M

Genes: 1956

Variants: L858R L861Q T790M

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EGFR mutants (R108K, T263P, A289V, G598V, L861Q) alter the molecular function of the EGF-signaling pathway, specifically showing increased tyrosine phosphorylation and differences in receptor downregulation in response to EGF stimulation.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Justification: Functional: The examination of other EGFR missense mutants (T263P, G598V, L861Q) also shows an increase in phosphotyrosine content, suggesting that these variants similarly affect the molecular function of the receptor.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage describes how NIH-3T3 cells expressing the EGFR missense mutants (R108K, T263P, A289V, G598V, and L861Q) produced large tumors in mice, indicating that these variants contribute to tumor development.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses the oncogenicity of EGFR missense mutations, indicating that the expression of these variants (R108K, T263P, A289V, G598V, and L861Q) in NIH-3T3 cells leads to anchorage-independent colony formation, a hallmark of tumorigenic behavior.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of specific EGFR missense mutations (R108K, T263P, A289V, and G598V) in gliomas, indicating their association with the disease and their representation in the receptor pool, which supports their use in defining or classifying the disease. Oncogenic: The mention of EGFR missense mutations in the context of gliomas suggests that these somatic variants contribute to tumor development or progression, as they are associated with the receptor pool in tumor samples.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Predisposing

Justification: Diagnostic: The passage discusses the identification of EGFR missense mutations in glioblastomas and their association with the disease, indicating that these mutations can be used to classify or define the tumor type. Oncogenic: The passage mentions that the identified EGFR mutations contribute to tumor development in glioblastomas, particularly noting the presence of somatic mutations in the tumor samples. Predisposing: The passage specifies that one of the mutations (E330K) was identified as germline, indicating it confers inherited risk for developing disease.

Gene→Variant (gene-first): 1956:A289 1956:A289D 1956:A289T 1956:E330K 1956:L861Q 1956:R108 1956:R324L

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 17

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the association of the R108K variant with clinical responses to EGFR kinase inhibitors, indicating a correlation with treatment response. Oncogenic: The R108K variant is identified in gliomas, suggesting its potential role in tumor development or progression, particularly in the context of EGFR amplification.

Gene→Variant (gene-first): 1956:R108K

Genes: 1956

Variants: R108K

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the presence of EGFR missense mutants, including L858R and L861Q, may sensitize transformed cells to EGFR kinase inhibitors, indicating a correlation with treatment response. Oncogenic: The identical missense mutations are described as having oncogenicity and playing a role in gliomagenesis, suggesting that these somatic variants contribute to tumor development.

Gene→Variant (gene-first): 1956:L858R 1956:L861Q 1956:T790M

Genes: 1956

Variants: L858R L861Q T790M

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the EGFR mutants (R108K, T263P, A289V, G598V, L861Q) alter the molecular function of the EGF-signaling pathway, specifically showing increased tyrosine phosphorylation and differences in receptor downregulation in response to EGF stimulation.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional

Justification: Functional: The examination of other EGFR missense mutants (T263P, G598V, L861Q) also shows an increase in phosphotyrosine content, suggesting that these variants similarly affect the molecular function of the receptor.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage describes how NIH-3T3 cells expressing the EGFR missense mutants (R108K, T263P, A289V, G598V, and L861Q) produced large tumors in mice, indicating that these variants contribute to tumor development.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses the oncogenicity of EGFR missense mutations, indicating that the expression of these variants (R108K, T263P, A289V, G598V, and L861Q) in NIH-3T3 cells leads to anchorage-independent colony formation, a hallmark of tumorigenic behavior.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:L861Q 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V L861Q R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of specific EGFR missense mutations (R108K, T263P, A289V, and G598V) in gliomas, indicating their association with the disease and their representation in the receptor pool, which supports their use in defining or classifying the disease. Oncogenic: The mention of EGFR missense mutations in the context of gliomas suggests that these somatic variants contribute to tumor development or progression, as they are associated with the receptor pool in tumor samples.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Predisposing

Justification: Diagnostic: The passage discusses the identification of EGFR missense mutations in glioblastomas and their association with the disease, indicating that these mutations can be used to classify or define the tumor type. Oncogenic: The passage mentions that the identified EGFR mutations contribute to tumor development in glioblastomas, particularly noting the presence of somatic mutations in the tumor samples. Predisposing: The passage specifies that one of the mutations (E330K) was identified as germline, indicating it confers inherited risk for developing disease.

Gene→Variant (gene-first): 1956:A289 1956:A289D 1956:A289T 1956:E330K 1956:L861Q 1956:R108 1956:R324L

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L