[Paper-level Aggregated] PMCID: PMC2670982

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The presence of somatic mutations, including L914F, which cause ligand-independent hyperphosphorylation and abnormal cellular responses, indicates a role in tumorigenesis related to venous malformations. Functional: The L914F mutation demonstrated abnormal localization and response to ligand when overexpressed in HUVECs, indicating a functional alteration in the receptor's activity.

Gene→Variant (gene-first): ANGPT1(284):L914F TEK(7010):R849W

Genes: ANGPT1(284) TEK(7010)

Variants: L914F R849W

[Paragraph-level] PMCID: PMC2670982 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predisposing, Oncogenic, Functional

Justification: Predisposing: The passage describes germline substitutions in the TIE2/TEK receptor that cause a rare inherited form of venous anomalies, indicating that these variants confer inherited risk for developing the disease. Oncogenic: The passage discusses somatic mutations in TIE2 that contribute to tumor development, specifically noting the identification of somatic mutations in lesions and their role in the etiology of sporadic venous malformations. Functional: The passage mentions that the L914F variant shows ligand-independent hyperphosphorylation and abnormal localization when overexpressed, indicating that it alters molecular function.

Gene→Variant (gene-first): 284:L914F 7010:R849W

Genes: 284 7010

Variants: L914F R849W