[Paragraph-level] PMCID: PMC1952070 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses mutations, including the L858R point mutation, in the context of their correlation with response to treatment, indicating a predictive relationship. Diagnostic: The mention of the L858R mutation as part of a group of mutations previously correlated with response suggests its role in defining or classifying a disease subtype.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC1952070 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses mutations, including the L858R point mutation, in the context of their correlation with response to treatment, indicating a predictive relationship. Diagnostic: The mention of the L858R mutation as part of a group of mutations previously correlated with response suggests its role in defining or classifying a disease subtype.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[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: 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: PMC8688876 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Diagnostic

Justification: Functional: The passage discusses how various KRAS variants, including both hotspot and non-hotspot mutations, exhibit distinct profiles and behaviors based on experimental measurements, indicating that these variants alter molecular or biochemical function. Diagnostic: The mention of clustering variants and their association with specific profiles suggests that these variants can be used to classify or define differences in behavior, which aligns with diagnostic evidence.

Gene→Variant (gene-first): 3845:A146T 3845:A146T/V 3265:A59T 3845:G12A/R 3845:G12A/R/S 3845:G12V/D 3845:G13C 3845:G13V/D 673:K177N 3845:L19F 3845:Q22K 3845:Q61 3845:Q61H 3845:Q61L/P 3845:R164Q 22882:T74P

Genes: 3845 3265 673 22882

Variants: A146T A146T/V A59T G12A/R G12A/R/S G12V/D G13C G13V/D K177N L19F Q22K Q61 Q61H Q61L/P R164Q T74P

[Paragraph-level] PMCID: PMC8688876 Section: RESULTS PassageIndex: 5

Evidence Type(s): Functional, Diagnostic

Justification: Functional: The passage discusses how various KRAS variants, including both hotspot and non-hotspot mutations, exhibit distinct profiles and behaviors based on experimental measurements, indicating that these variants alter molecular or biochemical function. Diagnostic: The mention of clustering variants and their association with specific profiles suggests that these variants can be used to classify or define differences in behavior, which aligns with diagnostic evidence.

Gene→Variant (gene-first): 3845:A146T 3845:A146T/V 3265:A59T 3845:G12A/R 3845:G12A/R/S 3845:G12V/D 3845:G13C 3845:G13V/D 673:K177N 3845:L19F 3845:Q22K 3845:Q61 3845:Q61H 3845:Q61L/P 3845:R164Q 22882:T74P

Genes: 3845 3265 673 22882

Variants: A146T A146T/V A59T G12A/R G12A/R/S G12V/D G13C G13V/D K177N L19F Q22K Q61 Q61H Q61L/P R164Q T74P

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the correlation of the rs3786362 variant with progression-free survival (PFS) and overall survival (OS) in mCRC patients, indicating its association with disease outcome independent of therapy. Diagnostic: The variant rs3786362 is used to classify patients based on their genotypes (AG/GG vs. AA), which suggests its role in defining or associating with a disease subtype in mCRC.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the association of the variant rs3786362 with reduced overall survival (OS) and progression-free survival (PFS), indicating its correlation with disease outcomes independent of therapy. Diagnostic: The variant rs3786362 is associated with different genotypes (AG and AA) that correlate with reduced PFS and OS, suggesting its role in classifying disease outcomes based on genotype.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that the rs3786362 G allele is significantly associated with progression-free survival (PFS) and overall survival (OS), which are outcomes related to disease prognosis. Diagnostic: The association of the rs3786362 G allele with tumor characteristics suggests it may be used to classify or define disease subtypes, particularly in colorectal cancer (CRC).

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the correlation of the rs3786362 variant with progression-free survival (PFS) and overall survival (OS) in mCRC patients, indicating its association with disease outcome independent of therapy. Diagnostic: The variant rs3786362 is used to classify patients based on their genotypes (AG/GG vs. AA), which suggests its role in defining or associating with a disease subtype in mCRC.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7545690 Section: RESULTS PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the association of the variant rs3786362 with reduced overall survival (OS) and progression-free survival (PFS), indicating its correlation with disease outcomes independent of therapy. Diagnostic: The variant rs3786362 is associated with different genotypes (AG and AA) that correlate with reduced PFS and OS, suggesting its role in classifying disease outcomes based on genotype.

Gene→Variant (gene-first): 7298:rs3786362

Genes: 7298

Variants: rs3786362

[Paragraph-level] PMCID: PMC7325368 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the response of patients with B-RAFV600E mutations to therapy, indicating a correlation between the variant and treatment outcomes in various cancers. Diagnostic: The mention of B-RAFV600E in the context of specific cancer types suggests its use as a biomarker to classify or define these diseases.

Gene→Variant (gene-first): 673:B-RAFV600E

Genes: 673

Variants: B-RAFV600E

[Paragraph-level] PMCID: PMC7325368 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the confirmed responses and stable disease (SD) in patients with K-RAS mutations, including G13D, indicating a correlation with treatment response. Diagnostic: The mention of K-RAS mutations, including G13D, in the context of specific cancer types (endometrial cancer and NSCLC) suggests its role in classifying or defining these diseases. Oncogenic: The reference to K-RAS mutations, including G13D, contributing to tumor development in specific cancer types supports the classification of this variant as oncogenic.

Gene→Variant (gene-first): 3845:G13D

Genes: 3845

Variants: G13D

[Paragraph-level] PMCID: PMC7325368 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the response of patients with B-RAFV600E mutations to therapy, indicating a correlation between the variant and treatment outcomes in various cancers. Diagnostic: The mention of B-RAFV600E in the context of specific cancer types suggests its use as a biomarker to classify or define these diseases.

Gene→Variant (gene-first): 673:B-RAFV600E

Genes: 673

Variants: B-RAFV600E

[Paragraph-level] PMCID: PMC7325368 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the confirmed responses and stable disease (SD) in patients with K-RAS mutations, including G13D, indicating a correlation with treatment response. Diagnostic: The mention of K-RAS mutations, including G13D, in the context of specific cancer types (endometrial cancer and NSCLC) suggests its role in classifying or defining these diseases. Oncogenic: The reference to K-RAS mutations, including G13D, contributing to tumor development in specific cancer types supports the classification of this variant as oncogenic.

Gene→Variant (gene-first): 3845:G13D

Genes: 3845

Variants: G13D

[Paragraph-level] PMCID: PMC8887939 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the overall response rate (ORR) and median progression-free survival (PFS) associated with the HER2 insertion mutations, indicating a correlation with treatment response. Diagnostic: The mention of the frequency of the HER2 Y772_A775dupYVMA mutation in patients suggests its role in defining or classifying a specific disease subtype.

Gene→Variant (gene-first): 2064:A775dupYVMA 2064:G776delinsVC

Genes: 2064

Variants: A775dupYVMA G776delinsVC

[Paragraph-level] PMCID: PMC8887939 Section: RESULTS PassageIndex: 11

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the overall response rate (ORR) and median progression-free survival (PFS) associated with the HER2 insertion mutations, indicating a correlation with treatment response. Diagnostic: The mention of the frequency of the HER2 Y772_A775dupYVMA mutation in patients suggests its role in defining or classifying a specific disease subtype.

Gene→Variant (gene-first): 2064:A775dupYVMA 2064:G776delinsVC

Genes: 2064

Variants: A775dupYVMA G776delinsVC

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 12

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage discusses how MDS with SF3B1 K700E mutations can be used to refine sub-classification and risk assessment criteria, indicating its role in defining or classifying a disease subtype. Prognostic: The passage states that MDS with SF3B1 K700E mutations is regarded to have a favorable prognosis, which correlates with disease outcome independent of therapy.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that SF3B1 K700E mutated MDS shows significantly better overall survival (OS) compared to non-K700E mutations, suggesting a correlation with disease outcome. Diagnostic: The mention of distinct clinicopathological and genomic characteristics associated with K700E and non-K700E SF3B1 mutations implies that the mutation type is used for risk-assessment and classification of MDS.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of K700E and non-K700E mutations with specific patient characteristics and outcomes, indicating their role in classifying patients with MDS. Prognostic: The passage reports on overall survival outcomes associated with SF3B1 mutations, including K700E, indicating that these variants correlate with disease prognosis independent of therapy. Oncogenic: The mention of mutations such as K700E contributing to the classification of MDS and their association with specific patient outcomes suggests a role in tumor development or progression.

Gene→Variant (gene-first): 23451:K666 23451:K700 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the analysis of clinical-pathologic features and outcomes in MDS patients, specifically exploring differences between K700E and non-K700E variants, indicating a potential role in classification or association with disease characteristics. Oncogenic: The mention of analyzing the clinical-pathologic features of SF3B1mut patients, including K700E, suggests that this variant may contribute to tumor development or progression in the context of MDS.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage states that SF3B1 mutations, including K700E, have a favorable prognosis in myelodysplastic syndromes, indicating a correlation with disease outcome. Diagnostic: The mention of SF3B1 mutations in the context of myelodysplastic syndromes suggests that these mutations, including K700E, are used to classify or define the disease.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that K700E SF3B1mut MDS showed a trend for longer overall survival (OS) compared to non-K700E SF3B1mut MDS, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The passage discusses the classification of K700E SF3B1mut MDS in relation to the proposed 2020 IWG-PM criteria, indicating its use in defining or classifying a disease subtype.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 19

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that K700E SF3B1mut MDS is associated with significantly better overall survival (OS) compared to SF3B1wt MDS, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The mention of K700E in the context of classifying MDS subtypes (e.g., comparing K700E SF3B1mut MDS to non-K700E SF3B1mut MDS) supports its role in defining or classifying a disease or subtype.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 18

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the overall survival (OS) rates of K700E SF3B1mut MDS patients compared to non-K700E patients, indicating a correlation with disease outcome independent of therapy. Diagnostic: The mention of K700E SF3B1mut MDS patients in relation to non-K700E patients suggests a classification or association with a specific disease subtype.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 16

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the overall survival (OS) outcomes of K700E SF3B1mut MDS patients compared to SF3B1wt patients, indicating that the K700E variant correlates with better disease outcomes independent of therapy. Diagnostic: The K700E variant is used to classify and differentiate between SF3B1mut and SF3B1wt MDS patients, indicating its role in defining disease subtypes.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the classification of patients based on the presence of the K700E variant, indicating its association with lower CCSS scores, which suggests a role in defining or classifying a disease subtype. Oncogenic: The mention of the K700E variant in the context of patients with MDS (myelodysplastic syndromes) implies its contribution to tumor development or progression, as it is associated with specific cytogenetic aberrations.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 10

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the clinico-pathologic features of MDS patients with K700E mutations, indicating that these mutations are associated with specific disease characteristics and classifications, such as higher percentages of ring sideroblasts and differences in IPSS-R categories. Oncogenic: The K700E mutation in SF3B1 is implicated in the classification of MDS patients and is associated with specific tumor characteristics, suggesting its role in tumor development or progression.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the frequency of specific mutations, including K666, K700E, and R625, in patients with MDS, indicating their association with the disease and their role in defining the mutational landscape. Oncogenic: The mention of SF3B1 mutations, including K700E, K666, and R625, as frequent mutations in patients with MDS suggests that these somatic variants contribute to tumor development or progression in this context.

Gene→Variant (gene-first): 23451:K666 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the mutational landscape of SF3B1 mutations, specifically mentioning the K700E subtype, which indicates its role in classifying or defining a disease subtype. Oncogenic: The mention of K700E in the context of SF3B1 mutations suggests its contribution to tumor development or progression, as it is associated with a specific subtype of myelodysplastic syndromes (MDS).

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 12

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage discusses how MDS with SF3B1 K700E mutations can be used to refine sub-classification and risk assessment criteria, indicating its role in defining or classifying a disease subtype. Prognostic: The passage states that MDS with SF3B1 K700E mutations is regarded to have a favorable prognosis, which correlates with disease outcome independent of therapy.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that SF3B1 K700E mutated MDS shows significantly better overall survival (OS) compared to non-K700E mutations, suggesting a correlation with disease outcome. Diagnostic: The mention of distinct clinicopathological and genomic characteristics associated with K700E and non-K700E SF3B1 mutations implies that the mutation type is used for risk-assessment and classification of MDS.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of K700E and non-K700E mutations with specific patient characteristics and outcomes, indicating their role in classifying patients with MDS. Prognostic: The passage reports on overall survival outcomes associated with SF3B1 mutations, including K700E, indicating that these variants correlate with disease prognosis independent of therapy. Oncogenic: The mention of mutations such as K700E contributing to the classification of MDS and their association with specific patient outcomes suggests a role in tumor development or progression.

Gene→Variant (gene-first): 23451:K666 23451:K700 23451:K700E 23451:R625

Genes: 23451

Variants: K666 K700 K700E R625

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the analysis of clinical-pathologic features and outcomes in MDS patients, specifically exploring differences between K700E and non-K700E variants, indicating a potential role in classification or association with disease characteristics. Oncogenic: The mention of analyzing the clinical-pathologic features of SF3B1mut patients, including K700E, suggests that this variant may contribute to tumor development or progression in the context of MDS.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10015977 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage states that SF3B1 mutations, including K700E, have a favorable prognosis in myelodysplastic syndromes, indicating a correlation with disease outcome. Diagnostic: The mention of SF3B1 mutations in the context of myelodysplastic syndromes suggests that these mutations, including K700E, are used to classify or define the disease.

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

Genes: 23451

Variants: K700E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage indicates that the presence of genetic alterations, including the NRAS G13C mutation, correlates with clinical benefit from treatment, suggesting a predictive relationship regarding therapy response. Diagnostic: The mention of the NRAS G13C mutation being detected in a patient implies its role in identifying or classifying the disease, which aligns with diagnostic evidence. Oncogenic: The NRAS G13C mutation is discussed in the context of being a mutation found in a patient, which suggests its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage indicates that BRAF V600E mutant ctDNA is detected in a significant proportion of patients, suggesting its use in defining or confirming the presence of a specific disease. Prognostic: The passage states that higher levels of ctDNA at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS), indicating a correlation with disease outcome independent of therapy. Oncogenic: The presence of the BRAF V600E variant in ctDNA suggests its role in tumor development or progression, as it is a known somatic mutation associated with cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that the non-colorectal cancer cohort included patients who were BRAF V600E mutation positive, indicating that this variant is used to classify or define a specific group of patients with selected cancers. Oncogenic: The BRAF V600E mutation is associated with tumor development in various cancers, as indicated by its presence in patients with selected cancers, suggesting its role in oncogenesis.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage indicates that the presence of genetic alterations, including the NRAS G13C mutation, correlates with clinical benefit from treatment, suggesting a predictive relationship regarding therapy response. Diagnostic: The mention of the NRAS G13C mutation being detected in a patient implies its role in identifying or classifying the disease, which aligns with diagnostic evidence. Oncogenic: The NRAS G13C mutation is discussed in the context of being a mutation found in a patient, which suggests its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage indicates that BRAF V600E mutant ctDNA is detected in a significant proportion of patients, suggesting its use in defining or confirming the presence of a specific disease. Prognostic: The passage states that higher levels of ctDNA at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS), indicating a correlation with disease outcome independent of therapy. Oncogenic: The presence of the BRAF V600E variant in ctDNA suggests its role in tumor development or progression, as it is a known somatic mutation associated with cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that the non-colorectal cancer cohort included patients who were BRAF V600E mutation positive, indicating that this variant is used to classify or define a specific group of patients with selected cancers. Oncogenic: The BRAF V600E mutation is associated with tumor development in various cancers, as indicated by its presence in patients with selected cancers, suggesting its role in oncogenesis.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

Genes: 1956

Variants: D770 G770 Y764insFQEA

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses patients with advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the variant is used to classify or define a specific disease subtype. Oncogenic: The mention of advanced lung cancers suggests that the G770 variant contributes to tumor development or progression, aligning with the definition of an oncogenic variant.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of the G770 variant in a cohort of cases with EGFR exon 20 insertion mutations, indicating its association with a specific mutation type and providing context for its classification. Oncogenic: The mention of the G770 variant in the context of EGFR mutations suggests its role in tumor development or progression, as it is part of a known oncogenic pathway associated with cancer.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic

Justification: Diagnostic: The mention of "frequency" in relation to "EGFR Exon 20 Insertions with a G770 Equivalence" suggests that the variant is being used to classify or define a specific disease or subtype.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the sensitivity of specific EGFR variants (D770 and G770) to various EGFR-TKIs, indicating a correlation with response to therapy. Diagnostic: The mention of EGFR exon 20 insertion mutations and their frequency in lung cancer suggests that these variants are used to classify and define a specific subtype of the disease. Oncogenic: The variants D770 and G770 are described as contributing to tumor development, as they are part of the EGFR mutations associated with lung cancer.

Gene→Variant (gene-first): 1956:D770 1956:G770 1956:Y764insFQEA

Genes: 1956

Variants: D770 G770 Y764insFQEA

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the correlation between the G770 variant and radiographic responses to therapies (poziotinib and mobocertinib) in advanced lung cancers, indicating its predictive nature regarding treatment response. Diagnostic: The mention of "EGFR exon 20 insertion mutations with G770 equivalence" suggests that the G770 variant is used to classify or define a specific subtype of lung cancer, supporting its role as a diagnostic marker.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses patients with advanced lung cancers harboring EGFR Exon 20 insertion mutations, indicating that the variant is used to classify or define a specific disease subtype. Oncogenic: The mention of advanced lung cancers suggests that the G770 variant contributes to tumor development or progression, aligning with the definition of an oncogenic variant.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of the G770 variant in a cohort of cases with EGFR exon 20 insertion mutations, indicating its association with a specific mutation type and providing context for its classification. Oncogenic: The mention of the G770 variant in the context of EGFR mutations suggests its role in tumor development or progression, as it is part of a known oncogenic pathway associated with cancer.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC8700411 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic

Justification: Diagnostic: The mention of "frequency" in relation to "EGFR Exon 20 Insertions with a G770 Equivalence" suggests that the variant is being used to classify or define a specific disease or subtype.

Gene→Variant (gene-first): 1956:G770

Genes: 1956

Variants: G770

[Paragraph-level] PMCID: PMC9338780 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the approval of combined therapy with dabrafenib plus trametinib for treatment of BRAF V600E-mutant anaplastic thyroid cancer, indicating a correlation with treatment response. Diagnostic: The mention of BRAF V600E as a specific mutation in anaplastic thyroid cancer suggests its role in defining or classifying the disease subtype.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC9338780 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the approval of combined therapy with dabrafenib plus trametinib for treatment of BRAF V600E-mutant anaplastic thyroid cancer, indicating a correlation with treatment response. Diagnostic: The mention of BRAF V600E as a specific mutation in anaplastic thyroid cancer suggests its role in defining or classifying the disease subtype.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in FGFR3, including K650 and N540, in the context of developmental syndromes such as bone dysplasia, indicating their association with specific disease states. Oncogenic: The mention of FGFR3 mutations, including K650 and N540, being prevalent in bladder cancer suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2261:K650 2261:N540 2261:N540K

Genes: 2261

Variants: K650 N540 N540K

[Paragraph-level] PMCID: PMC5029699 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in FGFR3, including K650 and N540, in the context of developmental syndromes such as bone dysplasia, indicating their association with specific disease states. Oncogenic: The mention of FGFR3 mutations, including K650 and N540, being prevalent in bladder cancer suggests that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 2261:K650 2261:N540 2261:N540K

Genes: 2261

Variants: K650 N540 N540K

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Diagnostic

Justification: Functional: The passage discusses how the ETV6 mutants (V345fs, N356fs, Y103fs, S105fs) are functionally inactive and lack transcriptional repression activity, indicating that these variants alter molecular function. Diagnostic: The passage mentions that ETV6-mutated cases have a characteristic gene expression signature and that all ETV6 mutant T-ALL samples were CD33 positive, suggesting that these variants are associated with a specific disease subtype.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC3244026 Section: RESULTS PassageIndex: 9

Evidence Type(s): Functional, Diagnostic

Justification: Functional: The passage discusses how the ETV6 mutants (V345fs, N356fs, Y103fs, S105fs) are functionally inactive and lack transcriptional repression activity, indicating that these variants alter molecular function. Diagnostic: The passage mentions that ETV6-mutated cases have a characteristic gene expression signature and that all ETV6 mutant T-ALL samples were CD33 positive, suggesting that these variants are associated with a specific disease subtype.

Gene→Variant (gene-first): 2120:N356fs 2120:S105fs 2120:V345fs 2120:Y103fs

Genes: 2120

Variants: N356fs S105fs V345fs Y103fs

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage describes the NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) variant as a somatic variant found in renal cell carcinomas (RCCs) and indicates its role in VHL-independent renal tumorigenesis, supporting its contribution to tumor development. Diagnostic: The passage discusses the search for germline ELOC variants in individuals with a VHL-like phenotype and indicates that the NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) variant was absent in these individuals, suggesting its potential use in defining or excluding a disease or subtype.

Gene→Variant (gene-first): 3091:c.236A>G 6921:c.261_272del 5979:c.274G>A 6921:c.311T>A 3855:c.74A>T 3855:p.Asp25Val 7409:p.Glu92Lys 6921:p.Leu104Gln 6921:p.Thr88_Pro91del 3091:p.Tyr79Cys

Genes: 3091 6921 5979 3855 7409

Variants: c.236A>G c.261_272del c.274G>A c.311T>A c.74A>T p.Asp25Val p.Glu92Lys p.Leu104Gln p.Thr88_Pro91del p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the identification of a de novo missense variant in ELOC and its validation in the proband, indicating its potential role in defining or confirming a genetic condition. Functional: The passage describes the critical role of the Tyr79 residue in forming a hydrogen bond within the pVHL alpha domain, suggesting that the variant alters molecular function.

Gene→Variant (gene-first): 3091:Tyr79 3091:Y79 3091:c.236A>G 3091:p.Tyr79Cys

Genes: 3091

Variants: Tyr79 Y79 c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses how the variant c.236A>G (p.Tyr79Cys) is associated with von Hippel-Lindau disease (VHL) and suggests that genetic testing for ELOC variants should be performed in individuals with suspected VHL disease, indicating its role in disease classification. Oncogenic: The variant is described as a de novo pathogenic variant identified in a proband with VHL disease and is linked to the development of renal cell carcinoma (RCC), suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 3091:c.236A>G 3091:p.Tyr79Cys

Genes: 3091

Variants: c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 9

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage describes the NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) variant as a somatic variant found in renal cell carcinomas (RCCs) and indicates its role in VHL-independent renal tumorigenesis, supporting its contribution to tumor development. Diagnostic: The passage discusses the search for germline ELOC variants in individuals with a VHL-like phenotype and indicates that the NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) variant was absent in these individuals, suggesting its potential use in defining or excluding a disease or subtype.

Gene→Variant (gene-first): 3091:c.236A>G 6921:c.261_272del 5979:c.274G>A 6921:c.311T>A 3855:c.74A>T 3855:p.Asp25Val 7409:p.Glu92Lys 6921:p.Leu104Gln 6921:p.Thr88_Pro91del 3091:p.Tyr79Cys

Genes: 3091 6921 5979 3855 7409

Variants: c.236A>G c.261_272del c.274G>A c.311T>A c.74A>T p.Asp25Val p.Glu92Lys p.Leu104Gln p.Thr88_Pro91del p.Tyr79Cys

[Paragraph-level] PMCID: PMC9402235 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the identification of a de novo missense variant in ELOC and its validation in the proband, indicating its potential role in defining or confirming a genetic condition. Functional: The passage describes the critical role of the Tyr79 residue in forming a hydrogen bond within the pVHL alpha domain, suggesting that the variant alters molecular function.

Gene→Variant (gene-first): 3091:Tyr79 3091:Y79 3091:c.236A>G 3091:p.Tyr79Cys

Genes: 3091

Variants: Tyr79 Y79 c.236A>G p.Tyr79Cys

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 16

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of PIK3CA mutations in patients with a clinical diagnosis of FAO, indicating that these variants are used to define or confirm the disease in these patients. Oncogenic: The PIK3CA mutations mentioned are somatic variants identified in primary fibroblasts, which suggests they contribute to tumor development or progression in the context of the patients' disease.

Gene→Variant (gene-first): 5294:3140 A>T 5290:c.3140 A>G 5290:c.3140 A>T 5290:p.H1047L 5290:p.H1047R

Genes: 5294 5290

Variants: 3140 A>T c.3140 A>G c.3140 A>T p.H1047L p.H1047R

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage confirms the presence of the c.241 G>A [p.E81K] mutation in the biopsies of a patient, indicating its role in defining or confirming the disease in that individual.

Gene→Variant (gene-first): 5290:c.241 G>A 5290:p.E81K

Genes: 5290

Variants: c.241 G>A p.E81K

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of the c.241 G>A [p.E81K] mutation in a specific patient, indicating its association with the patient's condition and its absence in the patient's parents, which suggests its role in defining or confirming a disease. Oncogenic: The mention of the mutation being detected in various tissues of the patient, particularly in the context of a mutational analysis, implies its potential contribution to tumor development or progression.

Gene→Variant (gene-first): 5290:c.241 G>A 5290:p.E81K

Genes: 5290

Variants: c.241 G>A p.E81K

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 16

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of PIK3CA mutations in patients with a clinical diagnosis of FAO, indicating that these variants are used to define or confirm the disease in these patients. Oncogenic: The PIK3CA mutations mentioned are somatic variants identified in primary fibroblasts, which suggests they contribute to tumor development or progression in the context of the patients' disease.

Gene→Variant (gene-first): 5294:3140 A>T 5290:c.3140 A>G 5290:c.3140 A>T 5290:p.H1047L 5290:p.H1047R

Genes: 5294 5290

Variants: 3140 A>T c.3140 A>G c.3140 A>T p.H1047L p.H1047R

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage confirms the presence of the c.241 G>A [p.E81K] mutation in the biopsies of a patient, indicating its role in defining or confirming the disease in that individual.

Gene→Variant (gene-first): 5290:c.241 G>A 5290:p.E81K

Genes: 5290

Variants: c.241 G>A p.E81K

[Paragraph-level] PMCID: PMC4411002 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of the c.241 G>A [p.E81K] mutation in a specific patient, indicating its association with the patient's condition and its absence in the patient's parents, which suggests its role in defining or confirming a disease. Oncogenic: The mention of the mutation being detected in various tissues of the patient, particularly in the context of a mutational analysis, implies its potential contribution to tumor development or progression.

Gene→Variant (gene-first): 5290:c.241 G>A 5290:p.E81K

Genes: 5290

Variants: c.241 G>A p.E81K

[Paragraph-level] PMCID: PMC12221223 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of mutational profiles in melanoma, specifically mentioning that C>T transitions are characterized as cutaneous melanoma-defining features, which indicates a role in classifying or defining the disease. Oncogenic: The mention of C>T transitions as part of the mutational profile in melanoma suggests that these somatic variants contribute to tumor development or progression, particularly in the context of melanoma.

Gene→Variant (gene-first): 4763:C>T

Genes: 4763

Variants: C>T

[Paragraph-level] PMCID: PMC12221223 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of mutational profiles in melanoma, specifically mentioning that C>T transitions are characterized as cutaneous melanoma-defining features, which indicates a role in classifying or defining the disease. Oncogenic: The mention of C>T transitions as part of the mutational profile in melanoma suggests that these somatic variants contribute to tumor development or progression, particularly in the context of melanoma.

Gene→Variant (gene-first): 4763:C>T

Genes: 4763

Variants: C>T

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 25

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of the H1047R PIK3CA mutation with specific tumor subtypes, indicating its role in classifying or defining disease characteristics in human samples. Oncogenic: The H1047R PIK3CA mutation is mentioned in the context of tumor analysis, suggesting its contribution to tumor development or progression as it is examined alongside other mutations in cancer samples.

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC10527017 Section: RESULTS PassageIndex: 25

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of the H1047R PIK3CA mutation with specific tumor subtypes, indicating its role in classifying or defining disease characteristics in human samples. Oncogenic: The H1047R PIK3CA mutation is mentioned in the context of tumor analysis, suggesting its contribution to tumor development or progression as it is examined alongside other mutations in cancer samples.

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

Genes: 5290

Variants: H1047R

[Paragraph-level] PMCID: PMC5792548 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the EGFR T790M mutation in the context of treatment response to osimeritinib and the development of resistance, indicating a correlation with therapy outcomes. Diagnostic: The passage states that the EGFR T790M mutation is used to identify patients with non-small cell lung cancer who are eligible for treatment with osimeritinib, thus classifying it as a diagnostic marker. Oncogenic: The EGFR T790M mutation is described as contributing to resistance in lung cancer, which implies its role in tumor progression and development.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5792548 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the EGFR T790M mutation in the context of treatment response to osimeritinib and the development of resistance, indicating a correlation with therapy outcomes. Diagnostic: The passage states that the EGFR T790M mutation is used to identify patients with non-small cell lung cancer who are eligible for treatment with osimeritinib, thus classifying it as a diagnostic marker. Oncogenic: The EGFR T790M mutation is described as contributing to resistance in lung cancer, which implies its role in tumor progression and development.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the identification and relative frequencies of K-Ras mutations in human colorectal tumors, indicating their association with the disease. Oncogenic: The mention of K-Ras mutations, including the V600E mutation, suggests their contribution to tumor development or progression, as they are associated with increased mutation frequency in the Ras pathway. Functional: The passage notes the predicted localization of each mutation in the functional domains of the K-Ras protein, indicating an alteration in molecular function.

Gene→Variant (gene-first): 3845:A to C 3845:Ala to Thr 3845:Arg to Gln 3845:C to T 3845:G to A 3845:Lys to Asn 673:V600E 3845:aspartic acid residue at codon 173

Genes: 3845 673

Variants: A to C Ala to Thr Arg to Gln C to T G to A Lys to Asn V600E aspartic acid residue at codon 173

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the detection of specific mutations in colorectal tumors, indicating their association with the disease, which supports their use in defining or classifying the disease. Oncogenic: The mention of mutations at codon 19 (G57T, Leu19Phe) and in B-Raf (V600E) suggests that these somatic variants may contribute to tumor development, as they are found in tumor samples.

Gene→Variant (gene-first): 673:G57T 3845:Leu19Phe 673:V600E

Genes: 673 3845

Variants: G57T Leu19Phe V600E

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Functional

Justification: Diagnostic: The passage discusses the identification and relative frequencies of K-Ras mutations in human colorectal tumors, indicating their association with the disease. Oncogenic: The mention of K-Ras mutations, including the V600E mutation, suggests their contribution to tumor development or progression, as they are associated with increased mutation frequency in the Ras pathway. Functional: The passage notes the predicted localization of each mutation in the functional domains of the K-Ras protein, indicating an alteration in molecular function.

Gene→Variant (gene-first): 3845:A to C 3845:Ala to Thr 3845:Arg to Gln 3845:C to T 3845:G to A 3845:Lys to Asn 673:V600E 3845:aspartic acid residue at codon 173

Genes: 3845 673

Variants: A to C Ala to Thr Arg to Gln C to T G to A Lys to Asn V600E aspartic acid residue at codon 173

[Paragraph-level] PMCID: PMC2837563 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the detection of specific mutations in colorectal tumors, indicating their association with the disease, which supports their use in defining or classifying the disease. Oncogenic: The mention of mutations at codon 19 (G57T, Leu19Phe) and in B-Raf (V600E) suggests that these somatic variants may contribute to tumor development, as they are found in tumor samples.

Gene→Variant (gene-first): 673:G57T 3845:Leu19Phe 673:V600E

Genes: 673 3845

Variants: G57T Leu19Phe V600E

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage mentions that patients with L858R mutations were included in a refined cohort, indicating that this variant is used to classify or define a specific group of patients with EGFR mutations in NSCLC. Prognostic: The passage discusses the progression-free survival (PFS) of patients with specific mutations, including L858R, suggesting that this variant correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage states that all 71 patients harbored baseline EGFR mutations, including specific variants, indicating their role in defining the patient cohort and confirming the presence of a disease subtype (NSCLC). Oncogenic: The mention of EGFR mutations, including G719C, L858R, and S768I, suggests that these somatic variants contribute to tumor development or progression in the context of non-small cell lung cancer (NSCLC).

Gene→Variant (gene-first): 1956:G719C 1956:L858R 1956:S768I

Genes: 1956

Variants: G719C L858R S768I

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage mentions that patients with L858R mutations were included in a refined cohort, indicating that this variant is used to classify or define a specific group of patients with EGFR mutations in NSCLC. Prognostic: The passage discusses the progression-free survival (PFS) of patients with specific mutations, including L858R, suggesting that this variant correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC9441062 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage states that all 71 patients harbored baseline EGFR mutations, including specific variants, indicating their role in defining the patient cohort and confirming the presence of a disease subtype (NSCLC). Oncogenic: The mention of EGFR mutations, including G719C, L858R, and S768I, suggests that these somatic variants contribute to tumor development or progression in the context of non-small cell lung cancer (NSCLC).

Gene→Variant (gene-first): 1956:G719C 1956:L858R 1956:S768I

Genes: 1956

Variants: G719C L858R S768I

[Paragraph-level] PMCID: PMC5355930 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage discusses the analysis of PIK3CA mutations to define patient subgroups, indicating that these variants are used to classify or associate with a disease or subtype. Prognostic: The mention of estimating median progression-free survival (PFS) for patient subgroups defined by PIK3CA mutations suggests a correlation with disease outcome independent of therapy.

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: PMC5355930 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Prognostic

Justification: Diagnostic: The passage discusses the analysis of PIK3CA mutations to define patient subgroups, indicating that these variants are used to classify or associate with a disease or subtype. Prognostic: The mention of estimating median progression-free survival (PFS) for patient subgroups defined by PIK3CA mutations suggests a correlation with disease outcome independent of therapy.

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

Genes: 5290

Variants: E542K E545K H1047R

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the detection of BRAF:p.V600E mutations in various tumor types, indicating its association with specific tumor classifications, which supports its use as a biomarker for diagnosis. Oncogenic: The H3F3A:p.K27M mutation is described as being present in specific tumor types, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 3021:p.K27M 673:p.V600E

Genes: 3021 673

Variants: p.K27M p.V600E

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage discusses the H3F3A:p.K27M mutation and BRAF:p.V600E mutation as recurrent abnormalities in specific tumor types, indicating their contribution to tumor development or progression. Diagnostic: The mention of BRAF:p.V600E mutations being frequent in pleomorphic xanthoastrocytomas suggests its use in defining or classifying this subtype of tumor.

Gene→Variant (gene-first): 3021:p.K27M 673:p.V600E

Genes: 3021 673

Variants: p.K27M p.V600E

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 11

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the detection of BRAF:p.V600E mutations in various tumor types, indicating its association with specific tumor classifications, which supports its use as a biomarker for diagnosis. Oncogenic: The H3F3A:p.K27M mutation is described as being present in specific tumor types, indicating its contribution to tumor development or progression.

Gene→Variant (gene-first): 3021:p.K27M 673:p.V600E

Genes: 3021 673

Variants: p.K27M p.V600E

[Paragraph-level] PMCID: PMC3727232 Section: RESULTS PassageIndex: 5

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage discusses the H3F3A:p.K27M mutation and BRAF:p.V600E mutation as recurrent abnormalities in specific tumor types, indicating their contribution to tumor development or progression. Diagnostic: The mention of BRAF:p.V600E mutations being frequent in pleomorphic xanthoastrocytomas suggests its use in defining or classifying this subtype of tumor.

Gene→Variant (gene-first): 3021:p.K27M 673:p.V600E

Genes: 3021 673

Variants: p.K27M p.V600E

[Paragraph-level] PMCID: PMC6938308 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage discusses somatic mutations in KRAS and BRAF, indicating that these variants contribute to tumor development as they are detected in specimens from patients with AVM. Diagnostic: The presence of specific mutations (G12D, G12V, V600E, Q636X) is used to classify and confirm the mutation status of patients, which is relevant for understanding their disease.

Gene→Variant (gene-first): 3845:G12D 3845:G12V 673:Q636X 673:V600E

Genes: 3845 673

Variants: G12D G12V Q636X V600E

[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: PMC6938308 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage discusses somatic mutations in KRAS and BRAF, indicating that these variants contribute to tumor development as they are detected in specimens from patients with AVM. Diagnostic: The presence of specific mutations (G12D, G12V, V600E, Q636X) is used to classify and confirm the mutation status of patients, which is relevant for understanding their disease.

Gene→Variant (gene-first): 3845:G12D 3845:G12V 673:Q636X 673:V600E

Genes: 3845 673

Variants: G12D G12V Q636X V600E

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 21

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in specific genes that are associated with druggable tyrosine kinase domains, indicating their relevance in defining or classifying disease subtypes. Oncogenic: The mention of mutations in tyrosine kinase domains suggests that these variants may contribute to tumor development or progression, particularly in the context of cancer-related mutations.

Gene→Variant (gene-first): 780:A829V 207:C77F 405:D735H 3084:E583D 2048:E924K 5156:M875L 780:R611C 208:S11F 3169:S375F 2064:V777L

Genes: 780 207 405 3084 2048 5156 208 3169 2064

Variants: A829V C77F D735H E583D E924K M875L R611C S11F S375F V777L

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that AGTR2 harbored two missense mutations (V184I and R251H) and describes AGTR2 as a gene associated with familial hypercholesterolemia, indicating its role in defining or classifying a disease. Oncogenic: The passage discusses mutations in AGTR2 and their potential involvement in angiotensin signaling and tissue fibrosis, which are relevant to tumor development or progression, suggesting a role in oncogenesis.

Gene→Variant (gene-first): 186:R251H 186:V184I

Genes: 186

Variants: R251H V184I

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 21

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in specific genes that are associated with druggable tyrosine kinase domains, indicating their relevance in defining or classifying disease subtypes. Oncogenic: The mention of mutations in tyrosine kinase domains suggests that these variants may contribute to tumor development or progression, particularly in the context of cancer-related mutations.

Gene→Variant (gene-first): 780:A829V 207:C77F 405:D735H 3084:E583D 2048:E924K 5156:M875L 780:R611C 208:S11F 3169:S375F 2064:V777L

Genes: 780 207 405 3084 2048 5156 208 3169 2064

Variants: A829V C77F D735H E583D E924K M875L R611C S11F S375F V777L

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that AGTR2 harbored two missense mutations (V184I and R251H) and describes AGTR2 as a gene associated with familial hypercholesterolemia, indicating its role in defining or classifying a disease. Oncogenic: The passage discusses mutations in AGTR2 and their potential involvement in angiotensin signaling and tissue fibrosis, which are relevant to tumor development or progression, suggesting a role in oncogenesis.

Gene→Variant (gene-first): 186:R251H 186:V184I

Genes: 186

Variants: R251H V184I

[Paragraph-level] PMCID: PMC7226056 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic, Prognostic

Justification: Diagnostic: The passage discusses the reclassification of glioma patients into different types based on expression levels and molecular alterations, indicating that these variants are used to define or classify the disease. Oncogenic: The mention of TERT mutation in gliomas suggests that this somatic variant may contribute to tumor development or progression, as it is associated with different expression levels in tumor types. Prognostic: The passage notes that molecular alterations in gliomas are linked to clinical phenotypes and can predict outcomes, such as overall survival, indicating a prognostic relationship.

Gene→Variant (gene-first): 7015:CGGA 94) in the TCGA

Genes: 7015

Variants: CGGA 94) in the TCGA

[Paragraph-level] PMCID: PMC7226056 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic, Prognostic

Justification: Diagnostic: The passage discusses the reclassification of glioma patients into different types based on expression levels and molecular alterations, indicating that these variants are used to define or classify the disease. Oncogenic: The mention of TERT mutation in gliomas suggests that this somatic variant may contribute to tumor development or progression, as it is associated with different expression levels in tumor types. Prognostic: The passage notes that molecular alterations in gliomas are linked to clinical phenotypes and can predict outcomes, such as overall survival, indicating a prognostic relationship.

Gene→Variant (gene-first): 7015:CGGA 94) in the TCGA

Genes: 7015

Variants: CGGA 94) in the TCGA

[Paragraph-level] PMCID: PMC7342819 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic, Predisposing, Oncogenic

Justification: Diagnostic: The passage discusses the identification of the KRAS p.G12V mutation and the PALB2 mutations in the context of a primary lesion, indicating their association with the disease. Predisposing: The PALB2 c.3114-1G>A mutation is explicitly described as a germline mutation detected in peripheral blood cells, suggesting it confers inherited risk for developing disease. Oncogenic: The PALB2 c.2514+1G>C mutation is described as a somatic mutation, which is associated with tumor development in the context of the primary lesion.

Gene→Variant (gene-first): 79728:c.2514+1G>C 79728:c.3114-1G>A 3845:p.G12V

Genes: 79728 3845

Variants: c.2514+1G>C c.3114-1G>A p.G12V

[Paragraph-level] PMCID: PMC7342819 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of a germline mutation (PALB2 c.3114-1G>A) and its association with the patient's diagnosis of pancreatic cancer, indicating its role in defining or confirming the disease. Oncogenic: The somatic mutation (PALB2 c.2514+1G>C) is mentioned in the context of molecular profiling, suggesting its contribution to tumor development or progression in the patient with pancreatic cancer.

Gene→Variant (gene-first): 79728:c.2514+1G>C 79728:c.3114-1G>A

Genes: 79728

Variants: c.2514+1G>C c.3114-1G>A

[Paragraph-level] PMCID: PMC7342819 Section: RESULTS PassageIndex: 2

Evidence Type(s): Diagnostic, Predisposing, Oncogenic

Justification: Diagnostic: The passage discusses the identification of the KRAS p.G12V mutation and the PALB2 mutations in the context of a primary lesion, indicating their association with the disease. Predisposing: The PALB2 c.3114-1G>A mutation is explicitly described as a germline mutation detected in peripheral blood cells, suggesting it confers inherited risk for developing disease. Oncogenic: The PALB2 c.2514+1G>C mutation is described as a somatic mutation, which is associated with tumor development in the context of the primary lesion.

Gene→Variant (gene-first): 79728:c.2514+1G>C 79728:c.3114-1G>A 3845:p.G12V

Genes: 79728 3845

Variants: c.2514+1G>C c.3114-1G>A p.G12V

[Paragraph-level] PMCID: PMC7099049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses how the number of risk genotypes (NRG) correlates with the hazard of death in patients with HNSCC, indicating a relationship between the variants and disease outcome. Diagnostic: The variants are used to define and classify patients into groups based on the number of risk genotypes, which is associated with survival outcomes in HNSCC.

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: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the association of specific SNP genotypes with survival outcomes in HNSCC, indicating that these variants correlate with risk of death independent of therapy. Diagnostic: The passage mentions the classification performance of risk genotypes of selected SNPs, suggesting their use in defining or classifying disease risk.

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: RESULTS PassageIndex: 7

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses how the number of risk genotypes (NRG) correlates with the hazard of death in patients with HNSCC, indicating a relationship between the variants and disease outcome. Diagnostic: The variants are used to define and classify patients into groups based on the number of risk genotypes, which is associated with survival outcomes in HNSCC.

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: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the association of specific SNP genotypes with survival outcomes in HNSCC, indicating that these variants correlate with risk of death independent of therapy. Diagnostic: The passage mentions the classification performance of risk genotypes of selected SNPs, suggesting their use in defining or classifying disease risk.

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

Genes: NA 388325 341019

Variants: rs16879870 rs2641256 rs2761591 rs854936

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of specific EGFR missense mutations (R108K, T263P, A289V, and G598V) in gliomas, indicating their association with the disease and their representation in the receptor pool, which supports their use in defining or classifying the disease. Oncogenic: The mention of EGFR missense mutations in the context of gliomas suggests that these somatic variants contribute to tumor development or progression, as they are associated with the receptor pool in tumor samples.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Predisposing

Justification: Diagnostic: The passage discusses the identification of EGFR missense mutations in glioblastomas and their association with the disease, indicating that these mutations can be used to classify or define the tumor type. Oncogenic: The passage mentions that the identified EGFR mutations contribute to tumor development in glioblastomas, particularly noting the presence of somatic mutations in the tumor samples. Predisposing: The passage specifies that one of the mutations (E330K) was identified as germline, indicating it confers inherited risk for developing disease.

Gene→Variant (gene-first): 1956:A289 1956:A289D 1956:A289T 1956:E330K 1956:L861Q 1956:R108 1956:R324L

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of specific EGFR missense mutations (R108K, T263P, A289V, and G598V) in gliomas, indicating their association with the disease and their representation in the receptor pool, which supports their use in defining or classifying the disease. Oncogenic: The mention of EGFR missense mutations in the context of gliomas suggests that these somatic variants contribute to tumor development or progression, as they are associated with the receptor pool in tumor samples.

Gene→Variant (gene-first): 1956:A289V 1956:G598V 1956:R108K 1956:T263P

Genes: 1956

Variants: A289V G598V R108K T263P

[Paragraph-level] PMCID: PMC1702556 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic, Predisposing

Justification: Diagnostic: The passage discusses the identification of EGFR missense mutations in glioblastomas and their association with the disease, indicating that these mutations can be used to classify or define the tumor type. Oncogenic: The passage mentions that the identified EGFR mutations contribute to tumor development in glioblastomas, particularly noting the presence of somatic mutations in the tumor samples. Predisposing: The passage specifies that one of the mutations (E330K) was identified as germline, indicating it confers inherited risk for developing disease.

Gene→Variant (gene-first): 1956:A289 1956:A289D 1956:A289T 1956:E330K 1956:L861Q 1956:R108 1956:R324L

Genes: 1956

Variants: A289 A289D A289T E330K L861Q R108 R324L

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 19

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of specific PIK3CA mutations in patients with distinct clinical features, indicating that these mutations are associated with certain syndromes, such as linear nevus sebaceous or Schimmelpenning syndrome and CLOVES syndrome. Oncogenic: The passage mentions that the PIK3CA mutations are "hotspot" mutations commonly seen in cancer, suggesting that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 5290:p.Glu542Lys 5290:p.Glu545Lys 5290:p.His1047Arg

Genes: 5290

Variants: p.Glu542Lys p.Glu545Lys p.His1047Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 17

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of the p.Glu453Lys and p.Gly914Arg mutations in patients with specific congenital conditions, indicating their association with the phenotypes observed, which supports their use in defining or classifying the disease. Oncogenic: The p.Glu453Lys and p.Gly914Arg mutations are described in the context of patients with congenital overgrowth syndromes, suggesting a role in tumor development or progression, particularly in the context of somatic mutations.

Gene→Variant (gene-first): 5290:p.Glu453Lys 5290:p.Gly914Arg

Genes: 5290

Variants: p.Glu453Lys p.Gly914Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 16

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of specific mutations (p.Arg93Gln, p.Gly106Val, p.Cys378Tyr) in patients with phenotypes that overlap with or suggest variants of MCAP, indicating that these mutations are associated with defining or classifying the disease. Oncogenic: The passage describes the mutations as somatic variants present in patients with specific phenotypes, suggesting their contribution to tumor development or progression, particularly in the context of the patients' conditions.

Gene→Variant (gene-first): 5290:p.Arg93Gln 5290:p.Cys378Tyr 5290:p.Gly106Val

Genes: 5290

Variants: p.Arg93Gln p.Cys378Tyr p.Gly106Val

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 14

Evidence Type(s): Diagnostic, Predisposing

Justification: Diagnostic: The passage discusses individuals with mosaic PIK3CA mutations, including the p.Glu726Lys variant, in the context of classic features of MCAP, indicating its role in defining or classifying the disease. Predisposing: The passage mentions that several patients with the p.Glu726Lys mutation had various clinical findings associated with MCAP, suggesting an inherited risk for developing this condition.

Gene→Variant (gene-first): 5290:p.Glu726Lys

Genes: 5290

Variants: p.Glu726Lys

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage discusses mutations that are proven or predicted to have a gain-of-function mechanism, indicating that these somatic variants contribute to tumor development or progression. Diagnostic: The mention of Glu545Ala and Glu545Lys mutations being detected in individuals with undefined "Cowden-like" features suggests an association with a specific disease or phenotype, supporting their use in diagnosis.

Gene→Variant (gene-first): 5290:Glu545Ala 5290:Glu545Lys 5290:p.Ala1035Thr 5290:p.Ala1035Val 5290:p.Asn345Lys 5290:p.Asn345Thr 5290:p.Gln546His 5290:p.Gln546Lys 5290:p.Gln546Pro 5290:p.Glu545Asp 5290:p.Glu545Gly 5290:p.Glu545Lys 5290:p.Tyr1021Cys 7249:p.Tyr1021His

Genes: 5290 7249

Variants: Glu545Ala Glu545Lys p.Ala1035Thr p.Ala1035Val p.Asn345Lys p.Asn345Thr p.Gln546His p.Gln546Lys p.Gln546Pro p.Glu545Asp p.Glu545Gly p.Glu545Lys p.Tyr1021Cys p.Tyr1021His

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of PIK3CA mutations with developmental pediatric disorders, indicating that these mutations are used to classify or define the disease phenotypes. Oncogenic: The mention of PIK3CA mutations, particularly the hotspot mutations, suggests their role in tumor development or progression, as they are frequently observed in affected individuals.

Gene→Variant (gene-first): 5290:p.Glu542Lys 5290:p.Glu545Lys 5290:p.Glu726Lys 5290:p.Gly914Arg 5290:p.His1047Arg

Genes: 5290

Variants: p.Glu542Lys p.Glu545Lys p.Glu726Lys p.Gly914Arg p.His1047Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic

Justification: Diagnostic: The passage discusses the identification of mutations in patients, including the p.Arg93Gln variant, suggesting its association with specific cases and indicating its role in defining or confirming a disease.

Gene→Variant (gene-first): 5290:p.Arg93Gln

Genes: 5290

Variants: p.Arg93Gln

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 19

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of specific PIK3CA mutations in patients with distinct clinical features, indicating that these mutations are associated with certain syndromes, such as linear nevus sebaceous or Schimmelpenning syndrome and CLOVES syndrome. Oncogenic: The passage mentions that the PIK3CA mutations are "hotspot" mutations commonly seen in cancer, suggesting that these somatic variants contribute to tumor development or progression.

Gene→Variant (gene-first): 5290:p.Glu542Lys 5290:p.Glu545Lys 5290:p.His1047Arg

Genes: 5290

Variants: p.Glu542Lys p.Glu545Lys p.His1047Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 17

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of the p.Glu453Lys and p.Gly914Arg mutations in patients with specific congenital conditions, indicating their association with the phenotypes observed, which supports their use in defining or classifying the disease. Oncogenic: The p.Glu453Lys and p.Gly914Arg mutations are described in the context of patients with congenital overgrowth syndromes, suggesting a role in tumor development or progression, particularly in the context of somatic mutations.

Gene→Variant (gene-first): 5290:p.Glu453Lys 5290:p.Gly914Arg

Genes: 5290

Variants: p.Glu453Lys p.Gly914Arg

[Paragraph-level] PMCID: PMC5019182 Section: RESULTS PassageIndex: 16

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of specific mutations (p.Arg93Gln, p.Gly106Val, p.Cys378Tyr) in patients with phenotypes that overlap with or suggest variants of MCAP, indicating that these mutations are associated with defining or classifying the disease. Oncogenic: The passage describes the mutations as somatic variants present in patients with specific phenotypes, suggesting their contribution to tumor development or progression, particularly in the context of the patients' conditions.

Gene→Variant (gene-first): 5290:p.Arg93Gln 5290:p.Cys378Tyr 5290:p.Gly106Val

Genes: 5290

Variants: p.Arg93Gln p.Cys378Tyr p.Gly106Val

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 11

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage discusses the presence of the p.M90I mutation in lung adenocarcinoma cell lines and its association with human primary lung adenocarcinomas, indicating that this somatic variant contributes to tumor development or progression. Diagnostic: The p.M90I mutation is mentioned as being seen in human primary lung adenocarcinomas, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): 6016:p.M90I

Genes: 6016

Variants: p.M90I

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of the RIT1 p.M90I variant in different cancer types, indicating its association with malignancies, which supports its use in defining or classifying disease subtypes. Oncogenic: The mention of somatic RIT1 mutations in myeloid malignancies and their overlap with mutations in lung adenocarcinoma suggests that these variants contribute to tumor development or progression.

Gene→Variant (gene-first): 6016:F82L 6016:M90I 6016:p.M90I

Genes: 6016

Variants: F82L M90I p.M90I

[Paragraph-level] PMCID: PMC4150988 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Predisposing

Justification: Diagnostic: The passage discusses the recurrent alteration of RIT1 alanine 77 and mentions that one of the mutated samples harbored a p.A77P mutation, indicating its association with tumor classification. Predisposing: The passage suggests that p.A77S may represent a rare germline variant, indicating a potential inherited risk for disease, although it is noted to be unlikely.

Gene→Variant (gene-first): NA:alanine 77 6016:p.A77P 6016:p.A77S

Genes: NA 6016

Variants: alanine 77 p.A77P p.A77S

[Paragraph-level] PMCID: PMC7081042 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses how certain HER2 mutations, such as S310F, S310Y, R678Q, D769H, and I767M, correlate with favorable outcomes and good responses to anti-HER2 therapy, indicating their predictive value for treatment efficacy. Diagnostic: The passage mentions the identification of HER2 SNPs in HER2-positive breast cancer patients and their relationship with clinical outcomes, suggesting that these variants can be used to classify or define the disease subtype. Oncogenic: The passage indicates that somatic mutations in HER2 are linked to resistance to anti-HER2 therapy, suggesting that these mutations contribute to tumor development or progression.

Gene→Variant (gene-first): 2064:D769H 2064:D769Y 2064:I767M 1956:K753I 2064:L755S 2064:R678Q 2064:S310F 2064:S310Y 2064:V842I

Genes: 2064 1956

Variants: D769H D769Y I767M K753I L755S R678Q S310F S310Y V842I

[Paragraph-level] PMCID: PMC4159563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The K27M-H3 mutation is described as being exclusively found in tumors with specific WHO grade II-IV astrocytoma histology, indicating its role in classifying and defining the disease subtype. Oncogenic: The passage indicates that the K27M-H3 mutation is associated with tumors that behave clinically as high-grade astrocytomas, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 90:K27M

Genes: 90

Variants: K27M

[Paragraph-level] PMCID: PMC8078423 Section: ABSTRACT PassageIndex: 8

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the improved overall survival (OS), objective response rate (ORR), and progression-free survival associated with the treatment of encorafenib plus cetuximab in patients with BRAF V600E mCRC, indicating a correlation with therapy response. Diagnostic: The mention of BRAF V600E in the context of metastatic colorectal cancer (mCRC) suggests its role in defining or classifying a specific disease subtype, as it is associated with a particular treatment regimen.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8078423 Section: ABSTRACT PassageIndex: 4

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses a trial involving patients with BRAF V600E-mutant mCRC and mentions endpoints related to overall survival (OS) and objective response rate (ORR), indicating a correlation with treatment response. Diagnostic: The mention of "BRAF V600E-mutant mCRC" implies that the variant is used to classify or define a specific subtype of cancer, which aligns with diagnostic evidence.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC8078423 Section: ABSTRACT PassageIndex: 2

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the correlation of the BRAFV600E variant with improved overall survival and objective response rate in patients treated with specific therapies, indicating its predictive value for treatment response. Diagnostic: The mention of BRAFV600E in the context of metastatic colorectal cancer suggests its role in defining or classifying a specific subtype of the disease, supporting its use as a diagnostic marker.

Gene→Variant (gene-first): 673:BRAFV600E

Genes: 673

Variants: BRAFV600E

[Paragraph-level] PMCID: PMC9365372 Section: RESULTS PassageIndex: 13

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the overall response rate (ORR) and disease control rate (DCR) in patients with the T790M variant, indicating a correlation with treatment response to abivertinib. Diagnostic: The mention of T790M+ in the context of evaluating patient cohorts suggests that this variant is used to classify or define a specific group of patients for treatment assessment.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC9365372 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage indicates that T790M-negative status was a major reason for exclusion from the study, suggesting its role in defining eligibility for treatment in patients with NSCLC. Predictive: The mention of T790M-negative status as a reason for screening failure implies that the presence of this variant may correlate with resistance to the treatment being studied (abivertinib).

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC8040738 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the use of combination targeted therapy with a selective BRAF inhibitor and MEK inhibitor for a patient with a BRAF mutation, indicating a correlation with treatment response. Diagnostic: The identification of BRAF alterations is mentioned as a means to assist clinicians in determining alternative targeted treatment strategies, suggesting its role in classifying or defining the tumor type. Oncogenic: The passage implies that the BRAF mutations contribute to tumor development or progression, as the patient has a ganglioglioma harboring a BRAF mutation.

Gene→Variant (gene-first): 673:V600E 673:p.T599dup 673:p.V600E

Genes: 673

Variants: V600E p.T599dup p.V600E

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the detection of the KRAS mutation c.34G>T (p.G12C) in NSCLC samples, indicating its association with the disease and its role in characterizing the mutation through sequencing. Oncogenic: The variant c.34G>T (p.G12C) is mentioned in the context of being a mutation detected in NSCLC samples, suggesting its contribution to tumor development or progression.

Gene→Variant (gene-first): 3845:c.34G>T 3845:p.G12C

Genes: 3845

Variants: c.34G>T p.G12C

[Paragraph-level] PMCID: PMC2766370 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of specific mutations (c.38G>A and delE746_A750) in the context of sequencing and testing, indicating their role in defining or confirming the presence of these mutations in the respective cell lines. Oncogenic: The mention of the delE746_A750 EGFR mutation in the context of tumor cell lines (NCI-H1650) suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 3845:c.38G>A 3845:delE746_A750 EGFR

Genes: 3845

Variants: c.38G>A delE746_A750 EGFR

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the efficacy of osimertinib as a potential treatment for patients harboring the p.L755P mutation, indicating a correlation with response to therapy. Diagnostic: The mention of "patients harboring these mutations" suggests that the p.L755P variant is used to classify or define a specific group of patients, indicating its role in diagnosis.

Gene→Variant (gene-first): 2064:p.L755P

Genes: 2064

Variants: p.L755P

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 5

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage indicates that the p.L755P mutation is associated with an effective response to the treatment with osimertinib in a patient with stage IV NSCLC. Diagnostic: The passage mentions that the patient harbors the p.L755P mutation, which is used to classify the patient's disease subtype (HER2 exon 19 mutation in NSCLC).

Gene→Variant (gene-first): 2064:p.L755P

Genes: 2064

Variants: p.L755P

[Paragraph-level] PMCID: PMC10183391 Section: RESULTS PassageIndex: 2

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses a patient treated with osimertinib, indicating that the variant correlates with a response to this specific therapy. Diagnostic: The variant is described as being present in a patient with stage IV NSCLC, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): 2064:c.2262_2264delinsTCC 2064:p.(L755P)

Genes: 2064

Variants: c.2262_2264delinsTCC p.(L755P)

[Paragraph-level] PMCID: PMC10183391 Section: ABSTRACT PassageIndex: 6

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the activity of osimertinib in a patient with the p.L755P mutation, indicating a correlation with treatment response. Diagnostic: The variant p.L755P is described as being present in a patient with NSCLC, suggesting its role in defining or classifying the disease.

Gene→Variant (gene-first): 2064:p.L755P

Genes: 2064

Variants: p.L755P

[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: 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: 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: 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: 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: 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: 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: 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: PMC5122709 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the effectiveness of BRAF inhibitors in patients with metastatic melanoma harboring BRAF V600 mutations, indicating a correlation with treatment response. Diagnostic: The BRAF V600 mutation is used to define and classify patients with metastatic melanoma, as all patients in the study had BRAFV600E mutations.

Gene→Variant (gene-first): 673:V600

Genes: 673

Variants: V600

[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: PMC4999563 Section: RESULTS PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the median progression-free survival (PFS) and overall survival (OS) associated with specific KRAS mutations, indicating a correlation with disease outcomes independent of therapy. Diagnostic: The mention of KRAS exon 2 mutant tumor subtypes suggests that these variants are used to classify or define a specific disease subtype.

Gene→Variant (gene-first): 3845:A146T 3845:G12C 3845:G12D 3845:G13D 3845:Q61H

Genes: 3845

Variants: A146T G12C G12D G13D Q61H

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage indicates that tumors carrying BRAF V600E mutations were identified, suggesting an association with the classification of the tumors. Oncogenic: The mention of BRAF V600E mutations in tumors implies a role in tumor development or progression, characteristic of oncogenic variants.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[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: PMC7611203 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the presence of specific pathogenic mutations in patients, indicating their association with disease, which supports the use of these variants for classification and diagnosis. Oncogenic: The mention of pathogenic mutations suggests that these variants contribute to tumor development or progression, particularly in the context of BRCA1 and BRCA2 mutations associated with cancer.

Gene→Variant (gene-first): 672:c.185delAG 672:c.5266dupC 675:c.5946delT 675:c.6174delT 672:c.68_69delAG

Genes: 672 675

Variants: c.185delAG c.5266dupC c.5946delT c.6174delT c.68_69delAG

[Paragraph-level] PMCID: PMC2360265 Section: RESULTS PassageIndex: 16

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses median overall survival (OS) in relation to the L858R mutation, indicating that there is no statistically significant difference in OS between patients with the L858R mutation and those with other mutations, which relates to disease outcome. Diagnostic: The mention of the L858R mutation in the context of comparing survival outcomes suggests its role in classifying or defining patient subgroups based on mutational status.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC2360265 Section: RESULTS PassageIndex: 14

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses time to tumor progression (TTP) in relation to different mutation groups, including L858R, indicating a correlation with disease outcome independent of therapy. Diagnostic: The mention of "classical mutations group" and comparisons with "wild-type" suggests that the L858R variant is used to classify or define a subtype of the disease.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC2360265 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the disease control rate (DCR) in relation to specific mutations, indicating a correlation between the presence of mutations (including L858R, G719D, and E746V) and treatment outcomes, which suggests predictive evidence regarding therapy response. Diagnostic: The mention of 'classical' mutations and their association with disease control rates implies that these mutations, including L858R, G719D, and E746V, are used to classify or define a subtype of the disease.

Gene→Variant (gene-first): 1956:E746V 1956:G719D 1956:L858R

Genes: 1956

Variants: E746V G719D L858R

[Paragraph-level] PMCID: PMC2360265 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the incidence of the L858R mutation in relation to patient demographics and histology, indicating its association with specific patient groups and suggesting its role in defining or classifying disease subtypes. Oncogenic: The mention of the L858R mutation in the context of 'classical mutations' and its presence in patients with tumors suggests that it contributes to tumor development or progression.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC2360265 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of patient groups based on their mutational status, specifically mentioning the presence of classical mutations such as G719D, E746V, and L858R, which are used to classify patients. Oncogenic: The passage indicates that the reported EGFR mutations, including G719D, E746V, and L858R, were found to be of somatic origin, suggesting their contribution to tumor development or progression.

Gene→Variant (gene-first): 1956:E746V 1956:G719D 1956:L858R

Genes: 1956

Variants: E746V G719D L858R

[Paragraph-level] PMCID: PMC2360265 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage discusses the association of classical mutations, including G719X and L858R, with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC, indicating a correlation with treatment response. Diagnostic: The mention of classical mutations in the EGFR tyrosine kinase domain being associated with sensitivity to TKIs suggests that these variants can be used to classify or define a subtype of disease in NSCLC patients.

Gene→Variant (gene-first): 1956:G719X 1956:L858R

Genes: 1956

Variants: G719X L858R

[Paragraph-level] PMCID: PMC5615879 Section: RESULTS PassageIndex: 16

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations identified in tumors located in the small intestine, indicating a significant association with the disease, which supports the use of these variants in defining or classifying the disease. Oncogenic: The passage describes mutations that contribute to tumor development, specifically mentioning internal tandem duplications and insertions in the context of tumors, indicating their role in oncogenesis.

Gene→Variant (gene-first): 3815:Ala-Tyr 3815:c.1504_1509 dup GCCTAT 3815:c.1509_1510insACCTAT 3815:p.Y503_F504insTY

Genes: 3815

Variants: Ala-Tyr c.1504_1509 dup GCCTAT c.1509_1510insACCTAT p.Y503_F504insTY

[Paragraph-level] PMCID: PMC5615879 Section: RESULTS PassageIndex: 13

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions specific variants and their occurrence in a case, indicating their association with a particular disease or condition. Oncogenic: The variants discussed are likely somatic mutations contributing to tumor development, as they are described in the context of a case study.

Gene→Variant (gene-first): 3815:K580dup 3815:c.1673_1674insTCC 3815:c.1731_1742dupTTATGATCACAA 3815:p.K558delinsBP

Genes: 3815

Variants: K580dup c.1673_1674insTCC c.1731_1742dupTTATGATCACAA p.K558delinsBP

[Paragraph-level] PMCID: PMC5615879 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage provides mutation frequencies for specific variants, indicating their association with a disease or subtype. Oncogenic: The mention of substitution mutations suggests that these variants may contribute to tumor development or progression, as they are likely somatic mutations.

Gene→Variant (gene-first): 3815:p.L576P 3815:p.T574I 3815:p.V559A 3815:p.V559D 3815:p.V560D 3815:p.V560G

Genes: 3815

Variants: p.L576P p.T574I p.V559A p.V559D p.V560D p.V560G

[Paragraph-level] PMCID: PMC5615879 Section: RESULTS PassageIndex: 10

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in exon 11 and their association with specific cases, indicating that these mutations can be used to classify or define a disease subtype. Oncogenic: The mention of double mutations and their role in the context of tumor development suggests that these somatic variants contribute to tumor progression.

Gene→Variant (gene-first): 728378:c.1666C>G 3815:c.1666_1668dupCAG 3815:c.1672_1677delAAGGTTinsAGT 728378:p.Q556E 3815:p.Q556dup

Genes: 728378 3815

Variants: c.1666C>G c.1666_1668dupCAG c.1672_1677delAAGGTTinsAGT p.Q556E p.Q556dup

[Paragraph-level] PMCID: PMC5615879 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the frequency of specific mutations, including in-frame deletions and substitutions, which are associated with the classification of cases, indicating their role in defining or confirming a disease subtype. Oncogenic: The mention of mutations in exon 11, including specific variants, suggests their contribution to tumor development or progression, as they are described in the context of cancer cases.

Gene→Variant (gene-first): 3815:K558 del 3815:V555del 3815:c.1669_1674delTGGAAG 3815:c.1676T>A 3815:c.1679T>A 3815:p.V559D 3815:p.V560D

Genes: 3815

Variants: K558 del V555del c.1669_1674delTGGAAG c.1676T>A c.1679T>A p.V559D p.V560D

[Paragraph-level] PMCID: PMC4823091 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Diagnostic

Justification: Predictive: The passage states that the L858R mutation sensitizes to inhibition by small molecule TKIs, indicating a correlation with response to therapy. Diagnostic: The L858R mutation is described as having the highest prevalence among activating EGFR kinase domain missense mutations, which suggests its use in defining or classifying a subtype of disease.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC3293822 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the conservation of mutated residues in the AR gene and their association with prostate cancer (PCa), indicating that these variants are used to classify or define a disease subtype. Functional: The passage mentions examining amino acids implicated in prostate cancer and suggests a possible role in the mechanics of AR function, indicating that these variants may alter molecular or biochemical function.

Gene→Variant (gene-first): 1387:A234 207:D221 367:D528 367:E198 2232:G142 367:G166 367:G524 367:L57 367:M523 367:M537 367:P269 2232:P340 367:P390 367:P514 10514:P515 367:P533 367:S296 367:S334

Genes: 1387 207 367 2232 10514

Variants: A234 D221 D528 E198 G142 G166 G524 L57 M523 M537 P269 P340 P390 P514 P515 P533 S296 S334

[Paragraph-level] PMCID: PMC3219854 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Oncogenic, Diagnostic

Justification: Oncogenic: The passage describes a missense point mutation (Trp557Gly) identified in the KIT gene associated with neurofibromatosis type 1-related gastrointestinal stromal tumors (GISTs), indicating its contribution to tumor development. Diagnostic: The variant Trp557Gly is mentioned in the context of identifying and characterizing the tumors associated with neurofibromatosis type 1, suggesting its role in defining the disease subtype.

Gene→Variant (gene-first): 3815:Trp557Gly

Genes: 3815

Variants: Trp557Gly

[Paragraph-level] PMCID: PMC4477877 Section: RESULTS PassageIndex: 12

Evidence Type(s): Diagnostic, Functional

Justification: Diagnostic: The passage discusses the identification of rare germline variants (V37M, R181H) in patients with B-ALL, indicating their association with the disease. Functional: Luciferase assays performed on the variants showed no significant changes in transcriptional repression activity compared to WT ETV6, indicating an assessment of their molecular function.

Gene→Variant (gene-first): 2120:11905459G>A 2120:12022436 G>A 2120:R181H 2120:V37M 2120:rs150089916

Genes: 2120

Variants: 11905459G>A 12022436 G>A R181H V37M rs150089916

[Paragraph-level] PMCID: PMC4477877 Section: RESULTS PassageIndex: 6

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the identification of a heterozygous deletion in ETV6 that is associated with the diagnosis of acute lymphoblastic leukemia (ALL) in the proband, indicating its role in defining the disease. Oncogenic: The variant N385fs is described as leading to a truncation of the ETV6 protein, which is implicated in tumor development, specifically in the context of acute lymphoblastic leukemia (ALL).

Gene→Variant (gene-first): 2120:N385fs 2120:c.1153-5_1153_1delAACAG

Genes: 2120

Variants: N385fs c.1153-5_1153_1delAACAG

[Paragraph-level] PMCID: PMC4477877 Section: RESULTS PassageIndex: 5

Evidence Type(s): Diagnostic, Predisposing, Oncogenic

Justification: Diagnostic: The variant 415 T>C is associated with thrombocytopenia and leukemia, as it was identified in all affected family members and absent in unaffected individuals, indicating its role in defining the disease. Predisposing: The passage describes the variant as being present in affected individuals and absent in unaffected individuals, suggesting it confers inherited risk for developing the disease, although it does not explicitly state that it is germline. Oncogenic: The variant is described in the context of leukemia, indicating its potential role in tumor development or progression, particularly as it is a missense mutation in a gene associated with leukemia.

Gene→Variant (gene-first): 10320:415 T>C 2120:L349P 2120:c. T1046C 2120:proline for leucine at codon 349

Genes: 10320 2120

Variants: 415 T>C L349P c. T1046C proline for leucine at codon 349

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 17

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses overall survival (OS) outcomes associated with the L858R variant, indicating that it correlates with disease outcome independent of therapy. Diagnostic: The mention of the type of EGFR mutation, including L858R, being associated with overall survival suggests its role in classifying or defining disease outcomes.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 13

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses overall survival (OS) in patients with the L858R variant, indicating a correlation between this variant and disease outcome, independent of therapy. Diagnostic: The mention of distinct survival patterns observed in different EGFR mutation subclasses, including L858R, suggests that this variant is used to classify or define a subtype of disease.

Gene→Variant (gene-first): 1956:L858R

Genes: 1956

Variants: L858R

[Paragraph-level] PMCID: PMC8307492 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the prevalence of EGFR mutations, including L858R and L861X, in patients at initial diagnosis, indicating their association with the disease and their use in defining the mutation status of patients. Oncogenic: The variants L858R and L861X are described as actionable mutations within the context of EGFR, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 1956:L858R 1956:L861X

Genes: 1956

Variants: L858R L861X