[Paper-level Aggregated] PMCID: PMC3244026

Evidence Type(s): Functional

Summary: Mutation: Y103fs | Summary: The Y103fs mutation leads to the expression of N-terminal truncated protein products and results in a functionally inactive ETV6 mutant, with no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6.

Evidence Type: Functional Mutation: S105fs | Summary: The S105fs mutation results in the activation of internal translation initiation sites and the expression of truncated ETV6 protein products, leading to a functionally inactive ETV6 mutant that shows no transcriptional repression activity and exhibits dominant-negative activity compared to wild-type ETV6.

Evidence Type: Functional Mutation: V345fs | Summary: The V345fs mutation causes the expression of C-terminal truncated polypeptides, resulting in a functionally inactive ETV6 mutant that shows no transcriptional repression activity and exhibits dominant-negative activity compared to wild-type ETV6.

Evidence Type: Functional Mutation: N356fs | Summary: The N356fs mutation results in the expression of C-terminal truncated ETV6 proteins, leading to a functionally inactive ETV6 mutant that demonstrates a lack of transcriptional repression activity and exhibits dominant-negative activity compared to wild-type ETV6.

Gene→Variant (gene-first): ETV6(2120):Y103fs ETV6(2120):S105fs ETV6(2120):V345fs ETV6(2120):N356fs

Genes: ETV6(2120)

Variants: Y103fs S105fs V345fs N356fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: V345fs | Summary: The V345fs ETV6 mutant is functionally inactive, showing no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6. Evidence Type: Functional | Mutation: N356fs | Summary: The N356fs ETV6 mutant is functionally inactive, demonstrating a lack of transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6. Evidence Type: Functional | Mutation: Y103fs | Summary: The Y103fs ETV6 mutant is functionally inactive, with no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6. Evidence Type: Functional | Mutation: S105fs | Summary: The S105fs ETV6 mutant is functionally inactive, showing no transcriptional repression activity and exhibiting dominant-negative activity compared to wild-type ETV6.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: Y103fs | Summary: The Y103fs mutation leads to the expression of N-terminal truncated protein products that alter the molecular function of the ETV6 protein. Evidence Type: Functional | Mutation: S105fs | Summary: The S105fs mutation results in the activation of internal translation initiation sites and the expression of truncated ETV6 protein products, indicating a change in molecular function. Evidence Type: Functional | Mutation: V345fs | Summary: The V345fs mutation causes the expression of C-terminal truncated polypeptides, which alters the molecular function of the ETV6 protein. Evidence Type: Functional | Mutation: N356fs | Summary: The N356fs mutation results in the expression of C-terminal truncated ETV6 proteins, indicating a change in molecular function.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paper-level Aggregated] PMCID: PMC3244026

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The text describes how ETV6 mutations (Y103fs, S105fs, V345fs, N356fs) result in functionally inactive proteins that lack transcriptional repression activity, indicating their functional consequences in the context of leukemia. Oncogenic: The presence of ETV6 mutations is associated with a characteristic gene expression signature in immature adult T cell leukemias, suggesting a role in leukemia development and indicating their oncogenic potential.

Gene→Variant (gene-first): ETV6(2120):N356fs ETV6(2120):S105fs ETV6(2120):V345fs ETV6(2120):Y103fs

Genes: ETV6(2120)

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Diagnostic

Justification: Functional: The passage discusses how the ETV6 mutants (V345fs, N356fs, Y103fs, S105fs) are functionally inactive and lack transcriptional repression activity, indicating that these variants alter molecular function. Diagnostic: The passage mentions that ETV6-mutated cases have a characteristic gene expression signature and that all ETV6 mutant T-ALL samples were CD33 positive, suggesting that these variants are associated with a specific disease subtype.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage describes how N-terminal and C-terminal truncating mutations in the ETV6 gene alter the expression of truncated protein products, indicating a change in molecular function. Oncogenic: The context of the mutations being associated with hematopoietic tumors suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Diagnostic

Justification: Functional: The passage discusses how the ETV6 mutants (V345fs, N356fs, Y103fs, S105fs) are functionally inactive and lack transcriptional repression activity, indicating that these variants alter molecular function. Diagnostic: The passage mentions that ETV6-mutated cases have a characteristic gene expression signature and that all ETV6 mutant T-ALL samples were CD33 positive, suggesting that these variants are associated with a specific disease subtype.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage describes how N-terminal and C-terminal truncating mutations in the ETV6 gene alter the expression of truncated protein products, indicating a change in molecular function. Oncogenic: The context of the mutations being associated with hematopoietic tumors suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs