[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Functional

Summary: Mutation: p.Glu542 | Summary: The p.Glu542 mutation in PIK3CA alters molecular function by increasing intracellular AKT phosphorylation, promoting cell survival and proliferation.

Evidence Type: Functional Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is associated with increased intracellular AKT phosphorylation, contributing to tumor development and progression.

Gene→Variant (gene-first): PIK3CA(5290):p.Glu542 PIK3CA(5290):H1047R

Genes: PIK3CA(5290)

Variants: p.Glu542 H1047R

[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Oncogenic

Summary: Mutation: E542K | Summary: The E542K mutation in PIK3CA is identified as a gain-of-function somatic mutation in the helical domain, contributing to tumor development in patients with macrodactyly.

Evidence Type: Oncogenic Mutation: H1047L | Summary: The H1047L mutation in PIK3CA is a somatic gain-of-function mutation located in the kinase domain, associated with tumor progression in macrodactyly patients.

Evidence Type: Oncogenic Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is a somatic mutation in the kinase domain, linked to increased intracellular AKT phosphorylation and contributing to tumor development and progression in macrodactyly patients.

Evidence Type: Oncogenic Mutation: R115P | Summary: The R115P mutation in PIK3CA is a somatic mutation present in lesional tissue but absent in blood, suggesting its role in tumor development in macrodactyly patients. It is located in a linker sequence and confirmed through exome sequencing.

Evidence Type: Oncogenic Mutation: R115L | Summary: The R115L mutation is associated with squamous cell carcinoma, indicating that mutations at p.Arg115 contribute to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.Arg115 | Summary: Mutations at p.Arg115 in PIK3CA are annotated in the context of cancer, indicating their potential role in oncogenesis.

Gene→Variant (gene-first): PIK3CA(5290):E542K PIK3CA(5290):H1047L PIK3CA(5290):H1047R PDK1(5163):R115P PIK3CA(5290):R115L PIK3CA(5290):p.Arg115

Genes: PIK3CA(5290) PDK1(5163)

Variants: E542K H1047L H1047R R115P R115L p.Arg115

[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Diagnostic

Summary: Mutation: R115P | Summary: The R115P mutation in PIK3CA is suggested as a likely candidate for macrodactyly, indicating its role in defining or classifying a disease.

Evidence Type: Diagnostic

Gene→Variant (gene-first): PDK1(5163):R115P

Genes: PDK1(5163)

Variants: R115P

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is associated with increased intracellular AKT phosphorylation, contributing to tumor development and progression. Evidence Type: Functional | Mutation: p.Glu542 | Summary: The p.Glu542 mutation in PIK3CA alters molecular function by increasing intracellular AKT phosphorylation, promoting cell survival and proliferation. Evidence Type: Oncogenic | Mutation: p.His1047 | Summary: The p.His1047 mutation in PIK3CA is linked to increased AKT phosphorylation, which is implicated in tumor development and progression.

Gene→Variant (gene-first): 5290:H1047R 5290:p.Glu542 5290:p.His1047

Genes: 5290

Variants: H1047R p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E542K | Summary: The E542K mutation is identified as a somatic mutation in the helical domain of PIK3CA, contributing to tumor development in macrodactyly patients. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation is a somatic mutation located in the kinase domain of PIK3CA, associated with tumor progression in macrodactyly patients. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation is a somatic mutation in the kinase domain of PIK3CA, contributing to tumor development in one of the macrodactyly patients. Evidence Type: Oncogenic | Mutation: R115P | Summary: The R115P mutation, identified through exome sequencing, is located in a linker sequence and is implicated in tumor development in macrodactyly patients.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P 5290:p.Glu542 5290:p.His1047

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Summary: Evidence Type: Diagnostic | Mutation: R115P | Summary: The R115P mutation in PIK3CA is suggested as a likely candidate for macrodactyly, indicating its role in defining or classifying a disease. Evidence Type: Oncogenic | Mutation: R115L | Summary: The R115L mutation is associated with a squamous cell carcinoma, suggesting that mutations at p.Arg115 contribute to tumor development or progression. Evidence Type: Oncogenic | Mutation: p.Arg115 | Summary: The annotation of mutations at p.Arg115 in the context of cancer indicates their potential role in oncogenesis.

Gene→Variant (gene-first): 5290:R115L 5163:R115P 5290:p.Arg115

Genes: 5290 5163

Variants: R115L R115P p.Arg115

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: C392G | Summary: The C392G variant in UBXN11 was identified as a candidate but was ultimately confirmed as a false positive, indicating it does not contribute to tumor development or progression. Evidence Type: Oncogenic | Mutation: R115P | Summary: The R115P mutation in PIK3CA was present in lesional tissue but absent in blood, suggesting it may contribute to tumor development or progression.

Gene→Variant (gene-first): 91544:C392G 5163:R115P

Genes: 91544 5163

Variants: C392G R115P

[Paragraph-level] PMCID: PMC3542862 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: E542K | Summary: The E542K mutation in PIK3CA is identified as a gain-of-function mutation contributing to tumor development in the affected nerve tissue of patients with macrodactyly. Evidence Type: Oncogenic | Mutation: H1047L | Summary: The H1047L mutation in PIK3CA is identified as a gain-of-function mutation contributing to tumor development in the affected nerve tissue of patients with macrodactyly. Evidence Type: Oncogenic | Mutation: H1047R | Summary: The H1047R mutation in PIK3CA is identified as a gain-of-function mutation contributing to tumor development in the affected nerve tissue of patients with macrodactyly. Evidence Type: Oncogenic | Mutation: R115P | Summary: The R115P mutation in PIK3CA is confirmed as a somatic mutation present in the affected nerve tissue, contributing to the pathophysiology of macrodactyly.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P

[Paper-level Aggregated] PMCID: PMC3542862

Evidence Type(s): Oncogenic, Functional, Predisposing

Justification: Oncogenic: The mutations in PIK3CA, including R115P, E542K, and H1047L/R, are described as gain-of-function mutations that activate the PI3K/AKT signaling pathway, which is known to be involved in cancer development. Functional: The presence of mutations such as R115P and E542K in PIK3CA leads to increased AKT activation, indicating a functional consequence of these mutations in the signaling pathway. Predisposing: The identification of somatic mutations in PIK3CA associated with macrodactyly suggests a genetic predisposition to this condition, as these mutations are linked to the activation of pathways involved in growth and development.

Gene→Variant (gene-first): UBXN11(91544):C392G PDK1(5163):R115P PIK3CA(5290):E542K PIK3CA(5290):H1047L PIK3CA(5290):H1047R PIK3CA(5290):p.Glu542 PIK3CA(5290):p.His1047 PIK3CA(5290):R115L PIK3CA(5290):p.Arg115

Genes: UBXN11(91544) PDK1(5163) PIK3CA(5290)

Variants: C392G R115P E542K H1047L H1047R p.Glu542 p.His1047 R115L p.Arg115

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how mutations at amino acids p.Glu542 and p.His1047 increase intracellular AKT phosphorylation, indicating an alteration in molecular function related to AKT activation. Oncogenic: The mention of increased AKT phosphorylation due to the H1047R mutation suggests that this somatic variant contributes to tumor development or progression by promoting cellular processes such as survival and proliferation.

Gene→Variant (gene-first): 5290:H1047R 5290:p.Glu542 5290:p.His1047

Genes: 5290

Variants: H1047R p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses somatic mutations in the PIK3CA gene, specifically mentioning that the E542K, H1047R, and H1047L mutations are known gain-of-function mutations frequently mutated in cancer, indicating their contribution to tumor development or progression. Functional: The passage notes that the mutations E542K and H1047 (both H1047R and H1047L) are located in the helical and kinase domains of the PI3K protein, which are known hotspots for somatic gain-of-function mutations, suggesting that these variants alter the molecular function of the protein.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P 5290:p.Glu542 5290:p.His1047

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The R115P mutation in PIK3CA is suggested as a likely candidate for macrodactyly, indicating its association with a specific disease. Oncogenic: The R115L mutation is annotated in a database of somatic mutations in cancer, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 5290:R115L 5163:R115P 5290:p.Arg115

Genes: 5290 5163

Variants: R115L R115P p.Arg115

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of the R115P mutation in PIK3CA in lesional tissue but not in blood, indicating its potential role in defining or confirming a disease state. Oncogenic: The R115P mutation in PIK3CA is described as potentially deleterious and is present in lesional tissue, suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 91544:C392G 5163:R115P

Genes: 91544 5163

Variants: C392G R115P

[Paragraph-level] PMCID: PMC3542862 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses somatic mutations in PIK3CA (including R115P, E542K, H1047L, and H1047R) that contribute to the pathophysiology of macrodactyly, indicating their role in tumor development or progression through activation of the PI3K/AKT signaling pathway. Functional: The passage mentions that the identified mutations lead to AKT activation, which indicates that these variants alter molecular or biochemical function related to cell signaling pathways.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how mutations at amino acids p.Glu542 and p.His1047 increase intracellular AKT phosphorylation, indicating an alteration in molecular function related to AKT activation. Oncogenic: The mention of increased AKT phosphorylation due to the H1047R mutation suggests that this somatic variant contributes to tumor development or progression by promoting cellular processes such as survival and proliferation.

Gene→Variant (gene-first): 5290:H1047R 5290:p.Glu542 5290:p.His1047

Genes: 5290

Variants: H1047R p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 6

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses somatic mutations in the PIK3CA gene, specifically mentioning that the E542K, H1047R, and H1047L mutations are known gain-of-function mutations frequently mutated in cancer, indicating their contribution to tumor development or progression. Functional: The passage notes that the mutations E542K and H1047 (both H1047R and H1047L) are located in the helical and kinase domains of the PI3K protein, which are known hotspots for somatic gain-of-function mutations, suggesting that these variants alter the molecular function of the protein.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P 5290:p.Glu542 5290:p.His1047

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P p.Glu542 p.His1047

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The R115P mutation in PIK3CA is suggested as a likely candidate for macrodactyly, indicating its association with a specific disease. Oncogenic: The R115L mutation is annotated in a database of somatic mutations in cancer, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 5290:R115L 5163:R115P 5290:p.Arg115

Genes: 5290 5163

Variants: R115L R115P p.Arg115

[Paragraph-level] PMCID: PMC3542862 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of the R115P mutation in PIK3CA in lesional tissue but not in blood, indicating its potential role in defining or confirming a disease state. Oncogenic: The R115P mutation in PIK3CA is described as potentially deleterious and is present in lesional tissue, suggesting it contributes to tumor development or progression.

Gene→Variant (gene-first): 91544:C392G 5163:R115P

Genes: 91544 5163

Variants: C392G R115P

[Paragraph-level] PMCID: PMC3542862 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses somatic mutations in PIK3CA (including R115P, E542K, H1047L, and H1047R) that contribute to the pathophysiology of macrodactyly, indicating their role in tumor development or progression through activation of the PI3K/AKT signaling pathway. Functional: The passage mentions that the identified mutations lead to AKT activation, which indicates that these variants alter molecular or biochemical function related to cell signaling pathways.

Gene→Variant (gene-first): 5290:E542K 5290:H1047L 5290:H1047R 5163:R115P

Genes: 5290 5163

Variants: E542K H1047L H1047R R115P