[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the KrasC118S mutation in the context of its role in carcinogenesis and tumor development, particularly in relation to urethane-induced lung tumors characterized by oncogenic Q61R/L mutations in Kras. Functional: The passage implies that the KrasC118S mutation alters the molecular behavior of Kras in the context of tumorigenesis, as it is assessed for its impact on carcinogenesis and tumor development.

Gene→Variant (gene-first): 4843:C118S 3845:Q61R/L

Genes: 4843 3845

Variants: C118S Q61R/L

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Prognostic

Justification: Oncogenic: The passage discusses the KrasC118S variant in the context of its role in mouse models, indicating that it does not lead to significant developmental or physiological defects, which suggests its involvement in tumor development or progression. Prognostic: The passage mentions the median lifespan of KrasC118S/C118S mice compared to Kras+/+ mice, indicating a potential correlation with disease outcome, although the difference was not statistically significant.

Gene→Variant (gene-first): 4843:C118S

Genes: 4843

Variants: C118S

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 6

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 4843:C118S

Genes: 4843

Variants: C118S

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the C118S mutation affects the ability of eNOS to stimulate the MAPK pathway and provides evidence of altered molecular function through immunoblot analysis of protein levels and activity. Oncogenic: The passage indicates that the C118S mutation is important for carcinogen-induced lung tumorigenesis, suggesting that it contributes to tumor development or progression.

Gene→Variant (gene-first): 4843:C118S 4843:G353>C 4846:S1177D

Genes: 4843 4846

Variants: C118S G353>C S1177D

[Paragraph-level] PMCID: PMC4234187 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the C118S mutation specifically blocks redox-dependent reactions that lead to Ras activation, indicating an alteration in molecular function. Oncogenic: The context of the study involves investigating the effect of the C118S mutation on Ras function during tumorigenesis, suggesting that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 4843:C118 4843:C118S 4843:G353 transversion to C 4843:G353>C

Genes: 4843

Variants: C118 C118S G353 transversion to C G353>C

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses mutations in the TK domain of EGFR that are critical for its activity, indicating that these variants alter molecular function related to protein activity. Oncogenic: The context of the mutations being in the TK domain of EGFR suggests that they may contribute to tumor development or progression, as this domain is often implicated in oncogenic signaling pathways.

Gene→Variant (gene-first): 1956:C797 NA:E734 NA:T785 1956:E868 1956:L858 1956:R831 NA:W731 1956:Y801

Genes: 1956 NA

Variants: C797 E734 T785 E868 L858 R831 W731 Y801

[Paragraph-level] PMCID: PMC2970593 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage states that the L858R mutation was found to increase sensitivity to the EGFR inhibitor, Erlotinib, indicating a correlation with treatment response. Oncogenic: All mutations mentioned in the passage, including C797Y, E734Q, E868G, L831H, L858R, T785A, W731L, and Y801H, are described as somatic mutations that contribute to tumor development, as they were identified in the tyrosine kinase domain of EGFR in cancer samples.

Gene→Variant (gene-first): 1956:C797Y 1956:E734Q 1956:E868G 1956:L831H 1956:L858R 1956:T785A 1956:W731L 1956:Y801H

Genes: 1956

Variants: C797Y E734Q E868G L831H L858R T785A W731L Y801H

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the SF3B1K700E mutation can be therapeutically targeted, indicating a correlation with treatment response to etoposide and olaparib, which are specific therapies. Oncogenic: The SF3B1K700E mutation is implicated in tumor development, as the passage describes its role in creating an HR defect and its effects on tumor growth in xenograft models.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses how the SF3B1 K700E variant contributes to cellular deficits characteristic of BRCA1/2 loss, indicating its role in tumor development or progression. Functional: The variant K700E is shown to alter the recruitment of Rad51 to replication forks and affects replication fork stability, demonstrating a change in molecular function.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the SF3B1K700E variant affects replication fork dynamics and efficiency of replication fork restart, indicating an alteration in molecular function related to DNA replication. Oncogenic: The context of the study involves assessing the impact of the SF3B1K700E mutation on cellular processes relevant to tumor development, such as replication fork dynamics, which suggests a role in oncogenesis.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The D210N variant is described as being catalytically inactivated, which alters its ability to resolve R-loops, indicating a change in molecular function. Oncogenic: The passage discusses the role of the D210N variant in the context of R-loop accumulation and genome instability, which are associated with tumor development and progression.

Gene→Variant (gene-first): 246243:D210N

Genes: 246243

Variants: D210N

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the K700E mutation alters molecular function by inducing unscheduled R-loops and affecting replication fork dynamics.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the SF3B1K700E mutation alters the molecular function of homologous recombination (HR) by affecting the formation and resolution of Rad51 foci, indicating a defect in the later stages of HR. Oncogenic: The SF3B1K700E mutation is implicated in tumor development or progression as it affects the ability of cells to resolve recombination intermediates, which is a critical process in maintaining genomic stability in cancer cells.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the SF3B1K700E variant alters the ability of cells to resolve DNA double-strand breaks (DSBs) and impairs homologous recombination (HR) repair, indicating a change in molecular function related to DNA repair mechanisms. Oncogenic: The SF3B1K700E mutation is described as cancer-associated and is shown to contribute to defects in DNA repair, which is a characteristic of oncogenic variants that promote tumor development or progression.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC7612475 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Functional

Justification: Predictive: The K700E mutation in SF3B1 increases cellular sensitivity to ionising radiation and various chemotherapeutic agents, including PARP inhibitors, indicating a correlation with treatment response. Functional: The K700E mutation alters HR efficiency and induces unscheduled R-loop formation, replication fork stalling, and defective replication fork restart, demonstrating an impact on molecular function.

Gene→Variant (gene-first): 23451:K700E

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC5355930 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Prognostic

Justification: Predictive: The passage suggests that patients with E545K/E542K mutations had shorter progression-free survival (PFS) and overall survival, indicating a potential role of these mutations in resistance to hormone therapy. Prognostic: The mention of shorter PFS and overall survival in patients with the E545K/E542K mutations indicates a correlation with disease outcome independent of therapy.

Gene→Variant (gene-first): 5290:E542K 5290:E545K

Genes: 5290

Variants: E542K E545K

[Paragraph-level] PMCID: PMC5355930 Section: RESULTS PassageIndex: 8

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the correlation between PIK3CA mutations (H1047R, E545K, E542K) and the efficacy of everolimus, indicating that these variants are associated with prolonged progression-free survival (PFS) in patients treated with this therapy. Oncogenic: The mention of PIK3CA mutations in the context of their role in tumor development and the efficacy of a cancer treatment suggests that these somatic variants contribute to tumor progression.

Gene→Variant (gene-first): 5290:E542K 5290:E545K 5290:H1047R

Genes: 5290

Variants: E542K E545K H1047R

[Paragraph-level] PMCID: PMC5355930 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage discusses the prevalence of PIK3CA mutations, including specific variants, in a patient population, indicating their association with the disease context. Predictive: The mention of higher prevalence of PIK3CA mutations in the everolimus arm compared to the placebo arm suggests a correlation with treatment response, indicating predictive value.

Gene→Variant (gene-first): 5290:E542K 5290:E545K 5290:H1047R

Genes: 5290

Variants: E542K E545K H1047R

[Paragraph-level] PMCID: PMC3184204 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predisposing, Diagnostic, Functional

Justification: Predisposing: The passage describes the discovery of the GATA2 gene as a predisposition gene for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), indicating that the variants are associated with inherited risk for developing these diseases. Diagnostic: The variants are used to define and classify familial forms of MDS and AML, as they are reported to segregate with the disease in multiple families, which supports their role in diagnosis. Functional: The passage mentions that the mutations have differential effects on transactivation of target genes, cellular differentiation, apoptosis, and global gene expression, indicating that they alter molecular or biochemical function.

Gene→Variant (gene-first): 2624:c.1061C>T 2624:c.1063_1065delACA 2624:p.Thr354Met 6688:p.Thr355del

Genes: 2624 6688

Variants: c.1061C>T c.1063_1065delACA p.Thr354Met p.Thr355del

[Paragraph-level] PMCID: PMC5613053 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the ability of gilteritinib to block mutated FLT3, including the D835Y and F691 mutations, and its correlation with improved survival in models of FLT3-driven AML, indicating a response to therapy. Oncogenic: The D835Y and F691 mutations in FLT3 are implicated in the pathogenesis of acute myeloid leukemia (AML), suggesting that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2322:D835Y 2322:F691

Genes: 2322

Variants: D835Y F691

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 25

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage discusses the classification of variants as Pathogenic and Likely Pathogenic, indicating their association with specific diseases or subtypes, which aligns with the definition of diagnostic evidence.

Gene→Variant (gene-first): 5728:A79T 5728:C211W 5728:E157G 5728:H123Q 5728:I135V 5728:I203V 5728:I400V 5728:K342N 5728:K402N 5728:L345V 5728:L70V 5728:M35V 5728:N117S 5728:N228S 5728:N340D 5728:N340H 5728:N356D 5728:P354Q 5728:Q298E 5728:S229T 5728:T202I 5728:T78A 5728:W274L 5728:Y176C 5728:Y180H 5728:Y65C

Genes: 5728

Variants: A79T C211W E157G H123Q I135V I203V I400V K342N K402N L345V L70V M35V N117S N228S N340D N340H N356D P354Q Q298E S229T T202I T78A W274L Y176C Y180H Y65C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including A126D, A126P, C124S, G129E, H123Q, P354Q, P38H, Q396R, R130L, and R130Q, alter the molecular function of PTEN by affecting pAKT levels, indicating changes in biochemical activity. Oncogenic: The variants are described in the context of their effects on the PI3-AKT signaling pathway and their ability to exhibit loss of function (LoF) or gain of function (GoF), which are indicative of their roles in tumor development or progression.

Gene→Variant (gene-first): 5728:A126D 5728:A126P 5728:C124S 5728:G129E 5728:H123Q 5728:P354Q 5728:P38H 5728:Q396R 5728:R130L 5728:R130Q

Genes: 5728

Variants: A126D A126P C124S G129E H123Q P354Q P38H Q396R R130L R130Q

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants affect protein stability and abundance, indicating that they alter molecular function, which is supported by the use of western blot analysis and flow cytometry to measure these changes.

Gene→Variant (gene-first): 5728:H93Y 5728:P354Q 5728:R130L 5728:R14G 5728:R15S 5728:T78A

Genes: 5728

Variants: H93Y P354Q R130L R14G R15S T78A

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how PTEN variants affect sensorimotor neural circuit function and chemotaxis in C. elegans, indicating that these variants alter molecular or biochemical function. Oncogenic: The context of the passage suggests that the PTEN variants are involved in a pathway related to tumor development or progression, particularly given the focus on mutations in a cancer-related gene.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:P354Q 5728:T167N 5728:Y176C

Genes: 5728

Variants: A79T C124S D268E G132D P354Q T167N Y176C

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including C124S, I101T, G132D, D268E, and A79T, alter neuronal growth processes and synapse density, indicating that these variants affect molecular or biochemical functions in neuronal cultures. Oncogenic: The passage mentions that the PHTS variant A79T exhibits a gain-of-function (GoF) phenotype in axonal growth, suggesting that it contributes to tumor development or progression in the context of its association with ASD.

Gene→Variant (gene-first): 5728:A79T 5728:C124S 5728:D268E 5728:G132D 5728:I101T

Genes: 5728

Variants: A79T C124S D268E G132D I101T

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how various PTEN variants, including C124S, G129E, N117S, and Q298E, alter developmental rates in Drosophila, indicating that these variants affect molecular or biochemical function related to insulin signaling and eclosion timing. Oncogenic: The mention of the known gain-of-function variant 4A inducing lethality suggests that some variants contribute to tumor development or progression, aligning with oncogenic behavior.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:N117S 5728:Q298E

Genes: 5728

Variants: C124S G129E N117S Q298E

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the C124S variant alters molecular interactions and functions within the context of PI3P metabolism and signaling, indicating a change in biochemical activity. Oncogenic: The C124S variant is described in the context of genetic interactions that may contribute to tumor development or progression, as it is involved in a synthetic dosage lethality screen related to PTEN's role in cancer biology.

Gene→Variant (gene-first): 5728:C124S

Genes: 5728

Variants: C124S

[Paragraph-level] PMCID: PMC7190743 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the classification of variants, including C124S, G129E, R130X, and R335X, in relation to their association with conditions such as ASD, PHTS, and somatic cancer, indicating their role in defining or confirming these diseases. Oncogenic: The passage mentions that C124S and G129E have been found in somatic cancer, indicating that these variants contribute to tumor development or progression. Functional: The passage describes several variants, including C124S and G129E, as having well-characterized disruptions on protein function, indicating that they alter molecular or biochemical function.

Gene→Variant (gene-first): 5728:C124S 5728:G129E 5728:R130X 5728:R335X 5728:Y138L

Genes: 5728

Variants: C124S G129E R130X R335X Y138L

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the relationship between p53 mutations (including R175H, R248W, R273H, R282W) and resistance to chemotherapy, specifically noting that cells with these mutations showed higher viability and increased IC50 for various drugs, indicating a correlation with drug resistance. Oncogenic: The passage implies that the p53 mutations contribute to tumor behavior by affecting cell response to chemotherapy, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 7157:R175H 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the association between p53 mutations (R248, R282) and the expression of CYP3A4, a drug metabolism enzyme, indicating a correlation with drug clearance and potential response to chemotherapeutic drugs. Functional: The passage describes how p53 mutations (R248, R282) alter the expression levels of the CYP3A4 enzyme, demonstrating a change in molecular function related to drug metabolism.

Gene→Variant (gene-first): 7157:R175 7157:R175H 7157:R248 7157:R248W 7157:R273 7157:R273H 7157:R282 7157:R282W

Genes: 7157

Variants: R175 R175H R248 R248W R273 R273H R282 R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 8

Evidence Type(s): Prognostic, Functional

Justification: Prognostic: The passage mentions that R248Q/W and R282W are associated with mortality, indicating a correlation with disease outcome. Functional: The passage discusses the enrichment of specific gene sets linked to cellular respiration and drug metabolism enzymes for certain mutations, suggesting alterations in molecular function.

Gene→Variant (gene-first): 7157:R175H 7157:R248Q/W 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248Q/W R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage indicates that the R282 mutation is associated with drug metabolism enzymes, suggesting its role in defining or classifying a specific biological context related to drug metabolism. Predictive: The mention of the R282 mutation in relation to drug metabolism enzymes implies a potential correlation with response or sensitivity to therapies that involve these enzymes.

Gene→Variant (gene-first): 7157:R282

Genes: 7157

Variants: R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses the association of R248 and R282 mutations with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Oncogenic: The mention of mice carrying the humanized mutation on R248 exhibiting significantly shorter survival time suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 7157:R175 7157:R248 7157:R273 7157:R282

Genes: 7157

Variants: R175 R248 R273 R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 4

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses how mutations at Arg248 and Arg282 correlate with significantly shorter overall survival times, indicating a relationship between these variants and disease outcome independent of therapy. Oncogenic: The mention of p53 mutations, including those at Arg248 and Arg282, suggests a role in tumor development or progression, as these mutations are associated with survival outcomes in cancer patients.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282 7157:G245 7157:R175 7157:R248 7157:R249S 7157:R273 7157:R282 7157:Y220

Genes: 7157

Variants: Arg248 Arg282 G245 R175 R248 R249S R273 R282 Y220

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 2

Evidence Type(s): Prognostic

Justification: Prognostic: The passage indicates that mutations at Arg282 and Arg248 are associated with shorter patient survival, which correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282

Genes: 7157

Variants: Arg248 Arg282

[Paragraph-level] PMCID: PMC5481739 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the somatic DNMT3A-V716F mutation and its predicted effect on methyltransferase activity, indicating that the variant alters molecular function. Oncogenic: The mention of the somatic DNMT3A-V716F mutation in the context of a tumor suggests that it contributes to tumor development or progression.

Gene→Variant (gene-first): 1788:V716F

Genes: 1788

Variants: V716F

[Paragraph-level] PMCID: PMC7293710 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how the KRASG12V mutation correlates with increased sensitivity to the antiproliferation therapy of metformin, indicating a predictive relationship between the variant and treatment response. Oncogenic: The KRASG12V mutation is implicated in tumor development as it is mentioned in the context of its effect on cell viability and sensitivity to therapy in colorectal cancer cell lines.

Gene→Variant (gene-first): 3845:G12V

Genes: 3845

Variants: G12V

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 15

Evidence Type(s): Predictive, Oncogenic, Functional

Justification: Predictive: The passage discusses the response of KB1(L1363P)P mammary tumors to targeted therapies, indicating that these tumors responded significantly better to cisplatin and the PARP inhibitor AZD2461, which correlates the variant with treatment response. Oncogenic: The variant is associated with tumor development and progression, as it is discussed in the context of mammary tumors and their response to therapies, suggesting a role in cancer biology. Functional: The passage describes how the variant affects the ability of tumor cells to induce RAD51 foci in response to gamma-radiation, indicating an alteration in molecular function related to DNA repair mechanisms.

Gene→Variant (gene-first): 7158:L1363P 7158:p.L1363P

Genes: 7158

Variants: L1363P p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive

Justification: Predictive: The variant L1363P is associated with a response to cisplatin and PARP inhibition, indicating its correlation with treatment sensitivity.

Gene→Variant (gene-first): 7158:L1363P

Genes: 7158

Variants: L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 13

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses how KB1(L1363P)P mammary tumors are classified as predominantly carcinosarcomas, indicating that the variant is used to define and classify a specific tumor subtype. Oncogenic: The variant L1363P is associated with the development of carcinosarcomas, suggesting that it contributes to tumor progression and development, which aligns with oncogenic behavior.

Gene→Variant (gene-first): 7158:L1363P 7158:p.L1363P

Genes: 7158

Variants: L1363P p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that the variant L1363P is associated with mammary tumors exhibiting EMT-like phenotypes, suggesting a role in tumor development or progression.

Gene→Variant (gene-first): 7158:L1363P

Genes: 7158

Variants: L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses how the Brca1 p.L1363P variant contributes to tumor formation and accelerates tumor development in a mouse model, indicating its role in tumor progression. Functional: The passage indicates that the Brca1 p.L1363P variant has a functional defect that compromises BRCA1-mediated homologous recombination repair (HRR), suggesting an alteration in molecular function.

Gene→Variant (gene-first): 7158:L1363P 7158:p.L1363P

Genes: 7158

Variants: L1363P p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Justification: Oncogenic: The variant p.L1363P is associated with a defect in mammary tumor suppression, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses increased sensitivity to cisplatin and PARP1 inhibition in the context of the Brca1 p.L1363P variant, indicating a correlation with treatment response. Functional: The variant p.L1363P is shown to severely attenuate BRCA1-PALB2 binding, which alters the molecular function related to homologous recombination repair (HRR).

Gene→Variant (gene-first): 672:leucine to proline 7158:p.L1363P 672:p.L1407P

Genes: 672 7158

Variants: leucine to proline p.L1363P p.L1407P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the variant p.L1363P alters the binding ability of BRCA1 to PALB2 and affects its activity in homologous recombination repair (HRR), demonstrating a change in molecular function.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Justification: Functional: The passage discusses the evaluation of the functional consequences of the Brca1 p.L1363P variant, indicating that it alters molecular or biochemical function.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses a functional analysis of the Brca1 p.L1363P variant, indicating that it alters embryonic development and leads to growth defects in mice, which demonstrates its impact on molecular or biochemical function. Oncogenic: The analysis of the Brca1 p.L1363P variant in the context of embryonic development and its comparison to Brca1-null mice suggests that it may contribute to tumor development or progression, as it is associated with severe phenotypes similar to pathogenic mutations in Brca1.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage indicates that the homozygous variant p.L1363P in Brca1 leads to embryonic lethality in mice, suggesting that it contributes to tumor development or progression.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 3

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the variant p.L1407P disrupts the interaction of BRCA1 with PALB2 and predicts that it disables the alpha-helical structure of the coiled-coil domain, indicating an alteration in molecular function. Oncogenic: The use of CRISPR/Cas9 to model the BRCA1 variant in mice suggests that the variant contributes to tumor development or progression, as it is being studied in the context of a gene essential for embryonic development and cancer biology.

Gene→Variant (gene-first): 672:4220T>C 7158:p.L1363P 672:p.L1407P

Genes: 672 7158

Variants: 4220T>C p.L1363P p.L1407P

[Paragraph-level] PMCID: PMC7612117 Section: RESULTS PassageIndex: 2

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 7158:p.L1363P

Genes: 7158

Variants: p.L1363P

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage discusses the correlation of MIB-1 labeling indices with the diagnosis and grade of tumors, indicating that the K27M variant is associated with specific tumor classifications.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 5

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses the transformation of tumors associated with the K27M variant, indicating its role in tumor development and progression, particularly in the context of glioblastoma transformation.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC5822176 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of H3 K27M-mutant tumors and provides demographic information, indicating that the variant is associated with specific histological diagnoses and patient characteristics. Oncogenic: The mention of H3 K27M in the context of tumors suggests that this somatic variant contributes to tumor development or progression, as it is identified in mutant tumors.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC5822176 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage discusses the H3 K27M mutation's association with various tumor types, indicating its role in defining and classifying these tumors, particularly in pediatric and adult cohorts. Prognostic: The passage mentions survival outcomes for patients with H3 K27M-mutant tumors, comparing mean survival times between adults and pediatric patients, which indicates a correlation with disease outcome. Oncogenic: The H3 K27M mutation is described as contributing to tumor development in various glioma types, indicating its role as a somatic variant involved in tumor progression.

Gene→Variant (gene-first): 3417:K27M

Genes: 3417

Variants: K27M

[Paragraph-level] PMCID: PMC3288377 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the frequency of the p.K27M mutation in DIPGs and its association with this specific subtype of brain tumors, indicating its role in defining or classifying the disease. Oncogenic: The p.K27M and p.G34R mutations are described as somatic mutations found in pediatric gliomas, suggesting their contribution to tumor development or progression.

Gene→Variant (gene-first): 3021:p.G34R 3021:p.K27M

Genes: 3021

Variants: p.G34R p.K27M

[Paragraph-level] PMCID: PMC6368247 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the emergence of the ESR1 Y537S mutation in the context of resistance to CDK4/6 inhibitors, indicating a correlation with treatment response and resistance. Oncogenic: The mention of the ESR1 Y537S mutation as a new driver mutation suggests that it contributes to tumor development or progression, particularly in the context of breast cancer.

Gene→Variant (gene-first): 5728:Y537S

Genes: 5728

Variants: Y537S

[Paragraph-level] PMCID: PMC5122709 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses patients treated with BRAF inhibitors, specifically mentioning the BRAF V600E mutation, which correlates with response to these therapies. Diagnostic: The passage states that all patients tested positive for the BRAF V600E mutation, indicating its use in defining or confirming the presence of a specific subtype of melanoma. Oncogenic: The BRAF V600E mutation is implicated in the development of melanoma, suggesting its role as a somatic variant contributing to tumor progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC2789045 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the FGFR3 mutations (S249C, Y375C, and K652E) alter molecular signaling pathways, specifically the phosphorylation of various proteins, indicating a change in biochemical function. Oncogenic: The passage describes how the mutant FGFR3 variants induce morphological transformation, cell proliferation, and anchorage-independent growth, which are indicative of their role in tumor development and progression.

Gene→Variant (gene-first): 2261:K652E 2261:S249C 2261:Y375C

Genes: 2261

Variants: K652E S249C Y375C

[Paragraph-level] PMCID: PMC7099049 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Prognostic

Justification: Prognostic: The passage indicates that the SNPs are suggested to play a crucial role in the prognosis of HNSCC, which correlates with disease outcome.

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC7099049 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Prognostic, Functional

Justification: Prognostic: The passage discusses the association of SNPs with HNSCC survival, indicating that these variants correlate with disease outcome, specifically overall survival, independent of therapy. Functional: The passage mentions that the genotype of rs16879870 and rs854936 is significantly associated with the expression of specific genes in cancer tissues, suggesting that these variants alter molecular function.

Gene→Variant (gene-first): NA:rs16879870 388325:rs2641256 341019:rs2761591 NA:rs854936

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC9900321 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in treating pancreatic ductal adenocarcinoma, indicating a correlation between the Gly-to-Asp mutation and response to therapy. Oncogenic: The Gly-to-Asp mutation in the KRAS oncogene is described as contributing to tumor development in pancreatic ductal adenocarcinoma, as it is found in more than 90% of patients with this cancer type.

Gene→Variant (gene-first): 3845:Gly-to-Asp

Genes: 3845

Variants: Gly-to-Asp

[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: PMC4999563 Section: ABSTRACT PassageIndex: 9

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that KRAS G12C and G13D mutations are associated with inferior progression-free survival (PFS) and overall survival (OS) in mCRC patients, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The mention of KRAS mutations being associated with heterogeneous outcomes compared to unmutated tumors implies that these variants can be used to classify or define a disease subtype in mCRC.

Gene→Variant (gene-first): 3845:G12C 3845:G13D

Genes: 3845

Variants: G12C G13D

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the correlation of KRAS mutations, including specific variants like G12C and G13D, with inferior overall survival (OS) and progression-free survival (PFS), indicating their impact on disease outcome independent of therapy. Diagnostic: The passage mentions that mutations in KRAS were diagnosed in tumors, indicating that these mutations are used to classify or define the disease.

Gene→Variant (gene-first): 3845:G12C 3845:G12D 3845:G12V 3845:G13D

Genes: 3845

Variants: G12C G12D G12V G13D

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses how KRAS G12C and G13D mutations correlate with inferior progression-free and overall survival in metastatic colorectal cancer patients, indicating their prognostic significance. Diagnostic: The mention of KRAS mutations being associated with tumor characteristics suggests their role in classifying or defining the disease subtype in colorectal cancer.

Gene→Variant (gene-first): 3845:G12C 3845:G13D

Genes: 3845

Variants: G12C G13D

[Paragraph-level] PMCID: PMC9837058 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses how mutations in PIK3CA, including G1049R, H1047R, and M1043I/L, contribute to the activation of the PI3K pathway, indicating their role in tumor development or progression. Functional: The passage describes how specific mutations alter the conformation and binding properties of the p110alpha subunit, indicating that these variants affect molecular function related to PI3K activation.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047R 5290:M1043I/L

Genes: 5290

Variants: G1049R H1047R M1043I/L

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 19

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the H1047R variant alters the binding interactions and structural dynamics of the protein in response to pY binding, indicating a change in molecular function.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 18

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the H1047R and G1049R variants alter the molecular interactions and conformations within the kinase domain, indicating a change in biochemical function related to the protein's activity. Oncogenic: The evidence suggests that the H1047R and G1049R variants contribute to activation through disruption of the inhibitory conformation, which is indicative of their role in tumor development or progression.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047R 5290:M1043L 5290:N1068fs

Genes: 5290

Variants: G1049R H1047R M1043L N1068fs

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 17

Evidence Type(s): Functional

Justification: Functional: The passage discusses changes observed for the H1047R variant in the context of HDX-MS experiments, indicating that it alters molecular or biochemical function, specifically in terms of perturbations in conformation.

Gene→Variant (gene-first): 5290:H1047R

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how C-terminal mutations, including M1043L, H1047R, G1049R, and N1068fs, affect the inhibitory interaction with the C-terminus, indicating an alteration in molecular function. Oncogenic: The mention of "oncogenic mutation" in relation to M1043L, H1047R, and G1049R suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047R 5290:M1043L 5290:N1068fs

Genes: 5290

Variants: G1049R H1047R M1043L N1068fs

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the variants H1047R, G1049R, M1043L, and N1068fs alter membrane binding and ATPase activity, indicating changes in molecular function. Oncogenic: The variants are described in the context of their effects on membrane binding and ATPase activity, which suggests a role in tumor development or progression.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047R 5290:M1043L 5290:N1068fs

Genes: 5290

Variants: G1049R H1047R M1043L N1068fs

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 13

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the intrinsic ATPase activity of the p110alpha mutants, indicating that the variants G1049R, H1047R, and M1043L alter molecular function by exhibiting significantly increased ATPase activity compared to wild type. Oncogenic: The context of the passage implies that the variants are somatic mutations in a cancer-related gene, contributing to tumor development or progression through their altered biochemical activity.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047R 5290:M1043L 5290:N1068fs

Genes: 5290

Variants: G1049R H1047R M1043L N1068fs

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 12

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses frequent oncogenic mutants and their role in tumor samples, indicating that these variants contribute to tumor development or progression. Functional: The analysis of the mutants and their binding to full-length p85alpha suggests that these variants alter molecular or biochemical function, specifically in the context of their interaction with regulatory complexes.

Gene→Variant (gene-first): 5290:G1049R 5290:H1047R 5290:H1047R/L 5290:M1043L 5290:M1043L/I 5290:N1044K 5290:N1068fs

Genes: 5290

Variants: G1049R H1047R H1047R/L M1043L M1043L/I N1044K N1068fs

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the H1047R mutation in the context of its role in activating the kinase domain and increasing membrane binding, indicating its contribution to tumor development or progression. Functional: The passage describes how the H1047R mutation alters the molecular interactions and structural organization of the kinase domain, affecting its binding properties and functionality.

Gene→Variant (gene-first): 5290:H1047R 5290:His1047 5290:Met1043

Genes: 5290

Variants: H1047R His1047 Met1043

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses the E726K variant in the context of oncogenic mutations and its association with conformational changes that contribute to tumor development, indicating its role in cancer progression. Functional: The passage describes how the E726K variant leads to conformational changes affecting the interaction between the ABD and p85 with the catalytic core, suggesting an alteration in molecular function.

Gene→Variant (gene-first): 5290:E726K

Genes: 5290

Variants: E726K

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the N345K variant affects the molecular interactions and binding of the p110alpha/p85alpha complex to membranes, indicating an alteration in biochemical function.

Gene→Variant (gene-first): 5290:N345K

Genes: 5290

Variants: N345K

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 4

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses oncogenic mutants (N345K, G106V, and G118D) and their expected role in promoting ABD/iSH2 disengagement, indicating their contribution to tumor development or progression. Functional: The data suggests that the variants alter the dynamics of the ABD-p85 complex and its interaction with the p110alpha catalytic core, indicating a change in molecular function related to binding and mobility.

Gene→Variant (gene-first): 5290:G106V 5290:G118D 5290:N345K

Genes: 5290

Variants: G106V G118D N345K

[Paragraph-level] PMCID: PMC9837058 Section: RESULTS PassageIndex: 2

Evidence Type(s): Functional

Justification: Functional: The passage discusses the D915N mutation in the context of its effect on protein conformation and membrane binding, indicating that it alters molecular function as assessed by HDX-MS experiments.

Gene→Variant (gene-first): 5290:D915N

Genes: 5290

Variants: D915N

[Paragraph-level] PMCID: PMC6280667 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the correlation of mutations, including those in splicing components like ZRSR2, with sensitivity to various drugs, indicating a relationship between the variant and treatment response.

Gene→Variant (gene-first): 8233:serine/arginine

Genes: 8233

Variants: serine/arginine

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses the tumor forming capacity of cells expressing the ERBB2 E401G variant, indicating that this somatic variant contributes to tumor development as evidenced by increased tumor growth in vivo.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 16

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses the effects of the ERBB2 E401G and S310F variants on the proliferative and invasive capacities of cancer cells, indicating that these variants alter molecular or biochemical functions related to cell behavior. Oncogenic: The evaluation of the proliferative and invasive capacities of cells expressing the ERBB2 variants suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 15

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 14

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the variants E401G and S310F alter the phosphorylation of downstream signaling pathway proteins, indicating a change in molecular function related to the MAPK pathway. Oncogenic: The evidence suggests that the variants contribute to tumor development or progression by activating signaling pathways associated with cancer, specifically through the ERBB2 dimerization and its effects on downstream signaling.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 12

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the E401G and S310F mutations affect the dimer interface stability of the EGFR-HER2 complex, indicating that these variants alter molecular interactions and stability.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 11

Evidence Type(s): None

Justification: Not enough information in this passage.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional

Justification: Functional: The passage indicates that the variant p.(E401G) alters the stability of the ligand-free EGFR HER2 heterodimer, which suggests a change in molecular function.

Gene→Variant (gene-first): 2176:p.(E401G)

Genes: 2176

Variants: p.(E401G)

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the variants E401G and S310F lead to increased phosphorylation levels of HER2 and EGFR, indicating that these variants alter molecular function related to protein activity. Oncogenic: The context of the passage suggests that the variants E401G and S310F contribute to tumor development or progression by enhancing the phosphorylation of key HER family proteins involved in oncogenesis.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 8

Evidence Type(s): Functional

Justification: Functional: The passage discusses the identification of potential dimerization partners of the HER2 E401G protein, indicating that the variant alters molecular interactions.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 7

Evidence Type(s): Functional

Justification: Functional: The passage discusses how the variants S310F and E401G alter the C-terminal phosphorylation of HER2, indicating a change in molecular function.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 6

Evidence Type(s): Functional

Justification: Functional: The passage discusses the ability of the variants E321G, E401G, and S310F to form disulfide-linked dimers, indicating that these variants alter molecular function related to protein interactions.

Gene→Variant (gene-first): 7157:E321G 2176:E401G 2064:S310F

Genes: 7157 2176 2064

Variants: E321G E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional

Justification: Functional: The passage mentions the evaluation of mechanisms for multiple ERBB2 variants, including E321G, E401G, S310F, and D845A, which suggests that these variants are being assessed for their biochemical functions.

Gene→Variant (gene-first): 2064:D845A 7157:E321G 2176:E401G 2064:S310F

Genes: 2064 7157 2176

Variants: D845A E321G E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 4

Evidence Type(s): Functional

Justification: Functional: The passage indicates that ERBB2 E401G has functional properties similar to S310F, suggesting that these variants alter molecular or biochemical function.

Gene→Variant (gene-first): 2176:E401G 2064:S310F

Genes: 2176 2064

Variants: E401G S310F

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage describes the ERBB2 E401G variant as a somatic mutation that is associated with ERBB2 gene amplification, indicating its contribution to tumor development or progression. Functional: The passage mentions that multiple computational tools supported a deleterious effect of the ERBB2 E401G variant on the encoded gene product, suggesting that it alters molecular or biochemical function.

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC8881279 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage mentions the detection of the ERBB2 E401G variant of uncertain significance (VUS) in a patient, indicating its use in defining or classifying a disease context, specifically in a patient with cancer of unknown primary (CUP).

Gene→Variant (gene-first): 2176:E401G

Genes: 2176

Variants: E401G

[Paragraph-level] PMCID: PMC6938308 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage indicates that KRAS codon p.12G and BRAF codon p.600V somatic mutations have been linked to brain AVMs, suggesting their role in defining or classifying the disease. Oncogenic: The mention of likely somatic disease-causing mutations, including KRAS mutations (p.G12D and p.G12V) and BRAF mutations (p.V600E and p.Q636X), indicates that these variants contribute to tumor development or progression.

Gene→Variant (gene-first): 3845:p.12G 673:p.600V 3845:p.G12D 3845:p.G12V 673:p.Q636X 673:p.V600E

Genes: 3845 673

Variants: p.12G p.600V p.G12D p.G12V p.Q636X p.V600E

[Paragraph-level] PMCID: PMC8307492 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the association of the L858R variant with overall survival (OS) in patients treated with first-line EGFR inhibitors, indicating its relevance to treatment response. Oncogenic: The L858R variant is mentioned in the context of EGFR mutations in non-small-cell lung cancer (NSCLC), suggesting its role in tumor development or progression as part of the broader analysis of clinically actionable EGFR mutations.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC10805385 Section: RESULTS PassageIndex: 17

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The passage discusses the overexpression of HOXC10 in KRAS-mutant tumors, specifically mentioning the genotype KRAS G12C/TP53 G245V, indicating that these somatic variants contribute to tumor development or progression. Predictive: The passage mentions the efficacy of combined MEK/BET inhibitors causing tumor regression in KRAS-mutant patient-derived xenograft models, suggesting a correlation between the variants and response to therapy.

Gene→Variant (gene-first): 3845:G12C 7157:G245V

Genes: 3845 7157

Variants: G12C G245V

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of KRASG12D mutant MEFs to a drug combination, indicating that the variant is associated with resistance to growth inhibition by the therapies tested. Oncogenic: The KRASG12D variant is implicated in tumor behavior, as it is described in the context of MEFs (mouse embryonic fibroblasts) and their growth characteristics, suggesting a role in tumor development or progression.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of KRAS G12C-mutant cells to specific therapies, indicating a correlation between the variant and sensitivity to the drugs MRTX849/AMG510 and KPT9274. Oncogenic: The variant KRAS G12C is implicated in tumor development, as the passage describes its presence in cancer cell lines and their proliferation in response to treatment, suggesting a role in cancer progression.

Gene→Variant (gene-first): 3845:G12C

Genes: 3845

Variants: G12C

Never stop with your first good idea. Always strive to find a better one and continue until you have one that is still better.

find ways to include everything, find things that you might not have originally connected. This allows you to interpret other ideas.

come back to a situation. View it from multiple perspectives. Allow yourself to see something that you wouldn't have seen originally. Ask people how they feel or view it. Get other thoughts and opinions to avoid concluding on one thing without looking at it through someone else's view.

You are in control of how you feel, and see the world. By changing your perspective allows you to truly get in tune with your creative side. If you start to think about how more and more things are creative, everything will have some sort of creative meaning to you.

Not getting something the first time isn't a fail and doesn't make you failure. It shows that you have learned something and by continuing to try also shows you are willing to continue to learn more.

Many famous inventors or artists didn't stop trying. They faced obstacles that could cause most people to stop trying, instead by knowing who you are and who you can be is worth facing any obstacle.

Experts may take advantage of you because they think they are better than you because they did something creative and successful first

Never stop trying and don't let peoples opinions scare you.

There are no bad ideas. Thinking this way will cause you to stop thinking creatively because of being so scared to have a silly idea

Your brain cannot tell whether it is real or imaginary, so imagine and think in "crazy" creative ways to get your brain to start creating something you might not have without thinking in an almost unrealistic way.

Generating new ideas and thinking in different ways or about different things is good for your brain.

INTRODUCTION

topic:"danger" of change, function: perspective

topic: Reagan's perspective, function: perspective/timeline

topic: student debt, function: introduction

His description of paragraphs from 150 to 350 words is interesting with respect to the amount of material that will fit on a 3x5" inch card during the note taking process.

Another justification of the PageRank algorithm is that hyperlinks influence the index of a page. For example, if a page is referred to by multiple other pages (well cited), then it's deemed important and will have a higher PageRank.

It assumes there's a random user click on pages at random and not backtracking. The probability in the randomness is the PageRank.

The damping factor is the probability that the "random surfer" will get bored and move on to another page. The damping factor can personalize search results, making it difficult for people to manipulate the system in order to get a higher ranking.

Another goal of Google is a specification of the previous goal (improved search quality), as they want to create an improved searching experience for students.

The World Wide Web was originally created to facilitate academic research, and Google plans on creating a system that can support research activities as mentioned.

The biggest issue with previous Web Search engines, like the World Wide Web Worm and later Altavista was that they handled very limited queries per day. They ranged in the millions, starting from 2, 20, to 100m, which was expected because of the technology, but not the most efficient manner.

What Google proposes is the challenge of a search engine with efficient crawling technology, able to use storage efficiently, fast queries and sorting, etc. It's inevitable that the tasks will become harder as the demand for the Web increases, but Google is designed to be scaled to large data sets.

Improved search quality means that users searching can find exactly what it is they want. At the time, search engines weren't reliable and it was more than a myth for a search engine to find "almost anything on the Web".

"I didn't fully understand it at the time, but throughout my time as a freshman at Boston College I've realized that I have the power to alter myself for the better and broaden my perspective on life. For most of my high school experience, I was holding to antiquated thoughts that had an impact on the majority of my daily interactions. Throughout my life, growing up as a single child has affected the way am in social interactions. This was evident in high school class discussions, as I did not yet have the confidence to be talkative and participate even up until the spring term of my senior year."

"Specifically, when one of my classmates stated how he was struggling with the concept and another one of my classmates took the initiative to clarify it, I realized that that individual possibilities vary greatly among students."

"The need to engage with people in terms of evaluating them for the aim of acquiring a different point of view was one occasion this semester where the knowledge I received in class positively changed the way I approached an issue. I was patient enough to explore other perspectives, some of which disagreed with mine, so that I might learn about their opinions without bias or prejudice."

The Degé Kangyur contains

Why would hydrogen and oxygen need to be separated for?

atleast he isnt alone . seems like there is noone competing against eachother the teacher basically has it out for everyone

trying really hard to make himself stand out. spending alot of time on his work maybe going above and beyond. its all for nothing though teacher doesn't seem amused

he is transitioning from what he is going through to what he went through through the class. teacher seems pretty mean towards the students and a little bit aggressive

he thought he was doing well until he mispronounced ibm and learns that it was a mistake he shouldn't of made because of how the teacher was ridiculing every single student he was confused as to why the teacher was referring to objects as genders it just didn't make sense to him

feeling very scared. seems like he is regretting it a little bit?

going back to school at an old age just to learn french

he realized at this moment he was screwed becasue of the teachers attitude towards everyone. he was reminded of his childhood and how he felt towards his mother.

very sarcastic towards the student

hes feeling nervous apparently and is aware of his surroundings and kind of feels out of place.

https://www.youtube.com/watch?v=WC_emx04Vz4

Paragraph

Paragraph Tag

You have a lot of hobbies.

This is an odd way to begin a sentence, paragraph, and new section. I'm also pretty sure she should write out "twenty seven," rather than "27."

"Beer", Tom said. I was unsure whether the bartender truly noticed our appearance. Without further notice, he reacted on Tom's inquiry, drew the beer and cut it off. He seemed oddly absent, as if his mind where somewhere far away.

Everyone of teen titans was fighting the evil, but yet very respectful old blonde enemy called The Peroxide Blonde, who said: "jingle bells, jingle bells, jingle all the way", in a high pitched and powerfull voice, but big fat Alice, which was the greatest superhero of them all, was beginning to shake her milkshake to gain street credit to obtain the blue diamond's powers. I could feel the power increasing jumping on the trampolin next to her.

"Did you know him?" one of the men asked, more out of naked curiosity than of an actual interest in the emotional relations of a whore.

The bartender didn't answer him even though Tom asked very directly with a potent tone. He just looked absent-minded over our heads and spitted, "What's yours?" to a tall stranger who'd come in. "Rye," the funny looking tall fellow said. The bartender scooped the bottle and glass over the bar counter, and poured a glass of ice cold water.

"I'm ninety-six and he's sixty-nine," Tommy said in a joking tone.

"Ho! Ho! Ho!", the big whore were almost shaking of laughter. "She has a really pretty voice" I thought to myself. The other whores sat with blank stares and didn't seem find Tommy's joke funny at all.

"It's a lie", the peroxide blonde repeated, refusing to let Alice get away with accusing her of such a thing. She was proud of what she had said.

"It's true" said Alice in her nice voice which was the only thing nice about her. "And it doesn't make any difference to me whether you believe it or not because it's my belief and that is individual." She wasn't crying anymore because she just realized this herself while saying it out loud. She was calm because she had found comfort in the truth of her own words.

Tom was rude, and said: "The other way from you", in an arrogant voice. He walked away without looking back, annoyed with everyone at the station.

"You can interfere with this one," said the man and turned his eyes towards the cook. "He likes it," he said, obviously indicating that the cook was sexually disoriented.