Somatic Mutations in the Angiopoietin-Receptor TIE2 Can Cause Both Solitary and Multiple Sporadic Venous Malformations
[Paper-level Aggregated] PMCID: PMC2670982
Evidence Type(s): Functional
Summary: Mutation: L914F | Summary: The L914F mutation alters molecular function, as it shows ligand-independent hyperphosphorylation and abnormal localization in endothelial cells when overexpressed.
Gene→Variant (gene-first): ANGPT1(284):L914F
Genes: ANGPT1(284)
Variants: L914F
Somatic Mutations in the Angiopoietin-Receptor TIE2 Can Cause Both Solitary and Multiple Sporadic Venous Malformations
[Paper-level Aggregated] PMCID: PMC2670982
Evidence Type(s): Oncogenic
Summary: Mutation: L914F | Summary: The L914F mutation is identified as a somatic variant contributing to tumor development, associated with loss-of-function of the TIE2 receptor in a resected venous malformation.
Gene→Variant (gene-first): ANGPT1(284):L914F
Genes: ANGPT1(284)
Variants: L914F
Somatic Mutations in the Angiopoietin-Receptor TIE2 Can Cause Both Solitary and Multiple Sporadic Venous Malformations
[Paper-level Aggregated] PMCID: PMC2670982
Evidence Type(s): Predisposing
Summary: Mutation: R849W | Summary: The R849W mutation is described as an inherited variant associated with a rare form of venous anomalies, indicating it confers inherited risk for disease.
Evidence Type: Predisposing
Gene→Variant (gene-first): TEK(7010):R849W
Genes: TEK(7010)
Variants: R849W
Germline substitutions in the endothelial cell tyrosine kinase receptor TIE2/TEK cause a rare inherited form of venous anomalies, mucocutaneous venous malformations (VMCM). We now identified a somatic 2nd hit causing los
[Paragraph-level] PMCID: PMC2670982 Section: ABSTRACT PassageIndex: 1
Evidence Type(s): Predisposing, Oncogenic, Functional
Summary: Evidence Type: Predisposing | Mutation: R849W | Summary: The R849W mutation is described as an inherited variant associated with a rare form of venous anomalies, indicating it confers inherited risk for disease. Evidence Type: Oncogenic | Mutation: L914F | Summary: The L914F mutation is identified as a somatic variant contributing to tumor development, as it is associated with loss-of-function of the TIE2 receptor in a resected venous malformation. Evidence Type: Functional | Mutation: L914F | Summary: The L914F mutation alters molecular function, as it shows ligand-independent hyperphosphorylation and abnormal localization in endothelial cells when overexpressed.
Gene→Variant (gene-first): 284:L914F 7010:R849W
Genes: 284 7010
Variants: L914F R849W
Somatic Mutations in the Angiopoietin-Receptor TIE2 Can Cause Both Solitary and Multiple Sporadic Venous Malformations
[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
Germline substitutions in the endothelial cell tyrosine kinase receptor TIE2/TEK cause a rare inherited form of venous anomalies, mucocutaneous venous malformations (VMCM). We now identified a somatic 2nd hit causing los
[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