[Paper-level Aggregated] PMCID: PMC2570525

Evidence Type(s): Oncogenic, Diagnostic, Functional

Justification: Oncogenic: The AKT1 E17K and AKT3 E17K mutations are described as activating mutations that lead to increased AKT phosphorylation, indicating their role in promoting cancer cell growth and survival. Diagnostic: The study utilized mass spectroscopy-based mutation detection to identify AKT1 E17K and AKT3 E17K mutations in melanoma specimens, demonstrating the potential for these mutations to serve as biomarkers for melanoma diagnosis. Functional: The expression of AKT3 E17K in human melanoma cells resulted in increased AKT phosphorylation, indicating that this mutation has a functional impact on cellular signaling pathways involved in cancer.

Gene→Variant (gene-first): AKT1(207):AKT1 (E17K AKT1(207):E17K AKT1(207):AKT1 E17K

Genes: AKT1(207)

Variants: AKT1 (E17K E17K AKT1 E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage describes how the AKT1 E17K variant alters molecular function by increasing AKT phosphorylation in NIH 3T3 cells and A375 human melanoma cells, indicating a change in biochemical activity. Oncogenic: The evidence suggests that the AKT1 E17K variant contributes to tumor development or progression, as it is expressed in a melanoma cell line and leads to increased AKT phosphorylation, which is often associated with oncogenic processes.

Gene→Variant (gene-first): 207:AKT1 E17K 207:E17K

Genes: 207

Variants: AKT1 E17K E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the E17K mutation activates AKT3, suggesting that it alters molecular or biochemical function.

Gene→Variant (gene-first): 207:E17K

Genes: 207

Variants: E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 4

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 207:AKT1 E17K 207:E17K

Genes: 207

Variants: AKT1 E17K E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of the E17K mutation in clinical specimens, indicating its association with melanoma and its presence in metastatic lesions, which supports its use in defining or classifying the disease. Oncogenic: The E17K mutation is described as being present in metastatic lesions, suggesting that it contributes to tumor development or progression in melanoma.

Gene→Variant (gene-first): 207:E17K

Genes: 207

Variants: E17K

[Paragraph-level] PMCID: PMC2570525 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions the detection of AKT1 E17K mutations in melanoma, indicating that the variant is associated with a specific disease (melanoma). Oncogenic: The mention of AKT1 E17K mutations in the context of melanoma suggests that this somatic variant may contribute to tumor development or progression.

Gene→Variant (gene-first): 207:AKT1 E17K 207:E17K

Genes: 207

Variants: AKT1 E17K E17K

[Paragraph-level] PMCID: PMC2570525 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the identification of the AKT1 (E17K) mutation in various cancer types, indicating its association with melanoma and suggesting its role in defining the presence of this mutation in cancer specimens. Oncogenic: The passage states that the AKT1 E17K mutation is an activating mutation that contributes to tumor development, as evidenced by its identification in melanoma specimens and cell lines, indicating its role in cancer progression. Functional: The passage mentions that the AKT3 E17K mutation results in the activation of AKT when expressed in human melanoma cells, demonstrating a change in molecular function related to the variant.

Gene→Variant (gene-first): 207:AKT1 (E17K 207:E17K

Genes: 207

Variants: AKT1 (E17K E17K

[Paragraph-level] PMCID: PMC2570525 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the identification of the AKT1 (E17K) mutation in various cancer types, indicating its association with melanoma and suggesting its role in defining the presence of this mutation in cancer specimens. Oncogenic: The passage states that the AKT1 E17K mutation is an activating mutation that contributes to tumor development, as evidenced by its identification in melanoma specimens and cell lines, indicating its role in cancer progression. Functional: The passage mentions that the AKT3 E17K mutation results in the activation of AKT when expressed in human melanoma cells, demonstrating a change in molecular function related to the variant.

Gene→Variant (gene-first): 207:AKT1 (E17K 207:E17K

Genes: 207

Variants: AKT1 (E17K E17K