[Paper-level Aggregated] PMCID: PMC6547725

Evidence Type(s): Functional

Summary: Mutation: p.Q22K | Summary: The p.Q22K mutation is associated with increased GTP loading, indicating an alteration in molecular or biochemical function.

Evidence Type: Functional Mutation: Gln61 | Summary: The residue Gln61 is involved in GTP hydrolysis and is likely affected by insertions that alter molecular interactions, impacting the protein's biochemical function. Additionally, insertions in Gln61 indicate alterations in molecular function related to GTP hydrolysis.

Evidence Type: Functional Mutation: p.Q61L | Summary: The functional consequences of the p.Q61L mutation in relation to RAS signaling indicate that it is a classic pathogenic missense mutation that may alter molecular function.

Evidence Type: Functional Mutation: p.G12V | Summary: The p.G12V variant alters the intrinsic dissociation rate of the nucleotide, shows reduced intrinsic GTP hydrolysis rates compared to wild type, and induces phosphorylation of ERK and AKT, indicating significant changes in molecular function and its role in RAS signaling pathways.

Gene→Variant (gene-first): KRAS(3845):p.Q22K RASA1(5921):Gln61 NRAS(4893):p.Q61L KRAS(3845):p.G12V

Genes: KRAS(3845) RASA1(5921) NRAS(4893)

Variants: p.Q22K Gln61 p.Q61L p.G12V

[Paper-level Aggregated] PMCID: PMC6547725

Evidence Type(s): Oncogenic

Summary: Mutation: p.G12A | Summary: The p.G12A mutation is described as affecting a classical position in the P-loop of KRAS, indicating its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.G13H | Summary: The p.G13H mutation is noted to affect a classical position in the P-loop of KRAS, suggesting its role in tumor development or progression.

Evidence Type: Oncogenic Mutation: p.Q61L | Summary: The p.Q61L mutation is described as a classic pathogenic missense mutation, suggesting its contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: p.G12V | Summary: The p.G12V variant is classified as a classical oncogenic variant, indicating its role in tumor development or progression. It alters the intrinsic dissociation rate of the nucleotide and enhances signaling capabilities, as evidenced by increased levels of phosphorylated ERK and AKT in transfected cells.

Evidence Type: Oncogenic Mutation: Gln61 | Summary: The mention of insertions in tumor samples at Gln61 suggests that these variants contribute to tumor development or progression, classifying them as oncogenic.

Gene→Variant (gene-first): KRAS(3845):p.G12A KRAS(3845):p.G13H NRAS(4893):p.Q61L KRAS(3845):p.G12V RASA1(5921):Gln61

Genes: KRAS(3845) NRAS(4893) RASA1(5921)

Variants: p.G12A p.G13H p.Q61L p.G12V Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 27

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: Gln61 | Summary: The passage discusses the impact of insertions on the catalytic Gln61, indicating that these variants alter molecular function related to GTP hydrolysis. Evidence Type: Oncogenic | Mutation: Gln61 | Summary: The mention of insertions in tumor samples suggests that these variants contribute to tumor development or progression, classifying them as oncogenic.

Gene→Variant (gene-first): 5921:Gln61

Genes: 5921

Variants: Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 25

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.G12V | Summary: The HRAS p.G12V variant alters molecular function by inducing phosphorylation of ERK and AKT, indicating its role in RAS signaling pathways. Evidence Type: Oncogenic | Mutation: p.G12V | Summary: The HRAS p.G12V variant contributes to tumor development by enhancing signaling capabilities, as evidenced by increased levels of phosphorylated ERK and AKT in transfected cells.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: p.G12V | Summary: The variant KRAS p.G12V is described as a classical oncogenic variant, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.G12V | Summary: The p.G12V variant of KRAS shows reduced intrinsic GTP hydrolysis rates compared to wild type, indicating an alteration in molecular function. Evidence Type: Oncogenic | Mutation: p.G12V | Summary: The p.G12V variant is classified as a classical oncogenic variant, contributing to tumor development and progression.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.G12V | Summary: KRAS p.G12V is described as a classical oncogenic variant, indicating its role in tumor development or progression. The variant's interaction with Raf-RBD and its altered dissociation rate further support its oncogenic properties. Evidence Type: Functional | Mutation: p.G12V | Summary: The variant KRAS p.G12V alters the intrinsic dissociation rate of the nucleotide, demonstrating a change in molecular function compared to wild type KRAS.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Summary: Evidence Type: Functional | Mutation: p.Q61L | Summary: The passage discusses the functional consequences of the p.Q61L mutation in relation to RAS signaling, indicating that it is a classic pathogenic missense mutation that may alter molecular function. Evidence Type: Oncogenic | Mutation: p.Q61L | Summary: The p.Q61L mutation is described as a classic pathogenic missense mutation, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 4893:p.Q61L

Genes: 4893

Variants: p.Q61L

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Summary: Evidence Type: Functional | Mutation: Gln61 | Summary: The residue Gln61 is involved in GTP hydrolysis and is likely affected by insertions that alter molecular interactions, impacting the protein's biochemical function.

Gene→Variant (gene-first): 5921:Gln61

Genes: 5921

Variants: Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: p.G12A | Summary: The p.G12A mutation is described as affecting a classical position in the P-loop of KRAS, indicating its contribution to tumor development or progression. Evidence Type: Oncogenic | Mutation: p.G13H | Summary: The p.G13H mutation is also noted to affect a classical position in the P-loop of KRAS, suggesting its role in tumor development or progression. Evidence Type: Functional | Mutation: p.Q22K | Summary: The p.Q22K mutation is associated with increased GTP loading, indicating an alteration in molecular or biochemical function.

Gene→Variant (gene-first): 3845:p.G12A 3845:p.G13H 3845:p.Q22K

Genes: 3845

Variants: p.G12A p.G13H p.Q22K

[Paper-level Aggregated] PMCID: PMC6547725

Evidence Type(s): Oncogenic, Functional, Predictive

Justification: Oncogenic: The text describes several RAS variants, including classical oncogenic mutations in KRAS and NRAS, and indicates that these mutations are associated with increased GTP loading and enhanced RAS signaling. Functional: The evidence discusses the impact of VMOS RAS variants on GTP hydrolysis and their interaction with GEFs and GAPs, suggesting alterations in their functional properties compared to wild type proteins. Predictive: The analysis of the VMOS RAS variants indicates potential changes in signaling capabilities, which could be used to predict the biological behavior of these variants in a clinical context.

Gene→Variant (gene-first): RASA1(5921):Gln61 KRAS(3845):p.G12A KRAS(3845):p.G13H KRAS(3845):p.Q22K KRAS(3845):p.G12V NRAS(4893):p.Q61L

Genes: RASA1(5921) KRAS(3845) NRAS(4893)

Variants: Gln61 p.G12A p.G13H p.Q22K p.G12V p.Q61L

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 27

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the impact of the insertions on the catalytic Gln61 might be stronger, indicating an alteration in molecular function related to GTP hydrolysis.

Gene→Variant (gene-first): 5921:Gln61

Genes: 5921

Variants: Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 25

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the HRAS p.G12V variant alters the signaling capability by affecting GTP hydrolysis and inducing phosphorylation of ERK and AKT, indicating a change in molecular function. Oncogenic: The HRAS p.G12V variant is implicated in inducing signaling pathways that are associated with tumor development, as evidenced by the increased levels of phosphorylated ERK and AKT in the transfected cells.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the classical oncogenic variant KRAS p.G12V in the context of its effect on GTP hydrolysis, indicating its role in tumor development or progression. Functional: The passage describes how the variant KRAS p.G12V affects the biochemical function of GTP hydrolysis, demonstrating its impact on molecular activity in the presence of RAS-GAP.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the p.G12V variant alters the intrinsic GTP hydrolysis rates, indicating a change in molecular function related to protein activity. Oncogenic: The p.G12V variant is described as a classical oncogenic variant, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: KRAS p.G12V is described as a classical oncogenic variant, indicating its contribution to tumor development or progression. Functional: The passage discusses how KRAS p.G12V alters the intrinsic dissociation rate of mGppNHp compared to wild type, indicating a change in molecular function.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the impact of the p.Q61L variant on nucleotide exchange, effector binding, and GTP hydrolysis, indicating that it alters molecular or biochemical function. Oncogenic: The p.Q61L variant is described as a classic pathogenic missense mutation, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 4893:p.Q61L

Genes: 4893

Variants: p.Q61L

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the insertions around Gln61 likely alter the molecular interactions and functions of the protein, particularly affecting GTP hydrolysis and interactions with GEFs and GAPs.

Gene→Variant (gene-first): 5921:Gln61

Genes: 5921

Variants: Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses mutations in RAS genes, including p.G12A, p.G13H, and p.Q22K, which are described as classical oncogenic mutations that affect tumor development and progression. Functional: The passage indicates that the p.Q22K mutation is associated with increased GTP loading, suggesting that it alters molecular function related to protein activity.

Gene→Variant (gene-first): 3845:p.G12A 3845:p.G13H 3845:p.Q22K

Genes: 3845

Variants: p.G12A p.G13H p.Q22K

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 27

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the impact of the insertions on the catalytic Gln61 might be stronger, indicating an alteration in molecular function related to GTP hydrolysis.

Gene→Variant (gene-first): 5921:Gln61

Genes: 5921

Variants: Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 25

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the HRAS p.G12V variant alters the signaling capability by affecting GTP hydrolysis and inducing phosphorylation of ERK and AKT, indicating a change in molecular function. Oncogenic: The HRAS p.G12V variant is implicated in inducing signaling pathways that are associated with tumor development, as evidenced by the increased levels of phosphorylated ERK and AKT in the transfected cells.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 22

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the classical oncogenic variant KRAS p.G12V in the context of its effect on GTP hydrolysis, indicating its role in tumor development or progression. Functional: The passage describes how the variant KRAS p.G12V affects the biochemical function of GTP hydrolysis, demonstrating its impact on molecular activity in the presence of RAS-GAP.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 21

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the p.G12V variant alters the intrinsic GTP hydrolysis rates, indicating a change in molecular function related to protein activity. Oncogenic: The p.G12V variant is described as a classical oncogenic variant, suggesting its role in tumor development or progression.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 18

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: KRAS p.G12V is described as a classical oncogenic variant, indicating its contribution to tumor development or progression. Functional: The passage discusses how KRAS p.G12V alters the intrinsic dissociation rate of mGppNHp compared to wild type, indicating a change in molecular function.

Gene→Variant (gene-first): 3845:p.G12V

Genes: 3845

Variants: p.G12V

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the impact of the p.Q61L variant on nucleotide exchange, effector binding, and GTP hydrolysis, indicating that it alters molecular or biochemical function. Oncogenic: The p.Q61L variant is described as a classic pathogenic missense mutation, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 4893:p.Q61L

Genes: 4893

Variants: p.Q61L

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the insertions around Gln61 likely alter the molecular interactions and functions of the protein, particularly affecting GTP hydrolysis and interactions with GEFs and GAPs.

Gene→Variant (gene-first): 5921:Gln61

Genes: 5921

Variants: Gln61

[Paragraph-level] PMCID: PMC6547725 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses mutations in RAS genes, including p.G12A, p.G13H, and p.Q22K, which are described as classical oncogenic mutations that affect tumor development and progression. Functional: The passage indicates that the p.Q22K mutation is associated with increased GTP loading, suggesting that it alters molecular function related to protein activity.

Gene→Variant (gene-first): 3845:p.G12A 3845:p.G13H 3845:p.Q22K

Genes: 3845

Variants: p.G12A p.G13H p.Q22K