Diagnostic, Oncogenic evidence:

Diagnostic: The study discusses the detection of PIK3CA mutations, including H1047L and H1047R, in various cancers, indicating their association with specific tumor types and mutation frequencies. This suggests that these variants can be used to classify or confirm the presence of disease in patients.

Oncogenic: The mention of PIK3CA mutations in the context of tumor detection implies that these variants, including H1047L and H1047R, contribute to tumor development or progression, as they are found in human tumors across different cancer types.

Diagnostic, Prognostic evidence:

Diagnostic: The study discusses the incidence of PIK3CA amplification in non-small cell lung cancer tissues and its association with specific patient demographics, indicating its role in classifying or defining a subtype of the disease.

Prognostic: The results highlight a significant difference in survival between patients with normal PIK3CA copy number and those with PIK3CA amplification, suggesting that this variant correlates with disease outcome independent of therapy.

Oncogenic, Functional evidence:

Oncogenic: The abstract discusses "recurrent genomic changes in lung tumors" and their "functional role," indicating that these changes contribute to tumor development or progression, which aligns with the definition of oncogenic variants.

Functional: The mention of "better understanding of cell growth, differentiation and apoptotic pathways" suggests that the genomic changes alter molecular or biochemical functions, supporting the classification as functional evidence.

Diagnostic, Oncogenic evidence:

Diagnostic: The study examines the association between PIK3CA gene copy number and tumor development stages, indicating that PIK3CA amplification is frequently observed in various lung cancer subtypes, which suggests its role in classifying or defining these diseases.

Oncogenic: The findings indicate that PIK3CA gene amplification is associated with lung tumorigenesis, suggesting that this somatic variant contributes to tumor development, particularly in squamous and small cell lung cancers.

Functional evidence:

Functional: The study discusses how PIK3CA mutations and copy number gains are associated with increased phosphatidylinositol 3-kinase activity and phosphorylated Akt expression, indicating that these alterations affect molecular function and cell growth. Additionally, the RNA interference-mediated knockdown of PIK3CA inhibited colony formation in cell lines with PIK3CA mutations, further supporting the functional impact of these variants.

Predictive, Diagnostic evidence:

Diagnostic: The study reports that PIK3CA mutations, including E545K, were identified in patients with lung adenocarcinoma, indicating that these mutations can be associated with this specific subtype of cancer.

Predictive: The abstract mentions that the impact of PIK3CA mutations on the efficacy of targeted therapies such as erlotinib and crizotinib is unknown, suggesting a potential correlation with treatment response, which aligns with predictive evidence.

Prognostic evidence:

Prognostic: The study reports that patients with concomitant PIK3CA mutations in exons 9 and 20 experienced significantly worse cancer-specific survival and overall survival compared to wild-type cases, indicating that these mutations correlate with disease outcome independent of therapy.

Oncogenic evidence:

Oncogenic: The abstract discusses mutations in the PIK3CA gene, specifically mentioning H1047R and H1047L, and indicates that these mutations are present in invasive breast carcinoma. The presence of these mutations suggests they contribute to tumor development, which aligns with the definition of oncogenic variants.

Diagnostic, Prognostic, Oncogenic evidence:

Diagnostic: The study investigates the frequency of PIK3CA mutations and amplifications in nasopharyngeal carcinoma (NPC), indicating that PIK3CA gene amplification is associated with advanced tumor stage and lymph node involvement, which helps classify the disease.

Prognostic: The findings show that patients with PIK3CA copy number gain have significantly reduced overall survival time, suggesting that this variant correlates with disease outcome independent of therapy.

Oncogenic: The study highlights that PIK3CA gene amplification is frequent in NPC and is associated with advanced disease, indicating its role in tumor development or progression.

Oncogenic evidence:

Oncogenic: The abstract states that the E542K variant, along with other mutants, is oncogenic in vivo, as it induces tumors in the chorioallantoic membrane of the chicken embryo and causes hemangiosarcomas, indicating its role in tumor development.

Oncogenic evidence:

Oncogenic: The abstract discusses the involvement of the PIK3CA gene and its common activating missense mutations in a variety of human tumor types, indicating that these mutations contribute to tumor development or progression. This aligns with the definition of oncogenic variants, which are known to drive cancer.

Predictive, Prognostic evidence:

Predictive: The study indicates that PIK3CA mutations were associated with shorter time to progression (TTP) in trastuzumab-treated breast cancer patients, suggesting a correlation with resistance to therapy. This aligns with the definition of predictive evidence, as it discusses the impact of the variant on treatment response.

Prognostic: The presence of PIK3CA mutations was linked to decreased survival from the initiation of trastuzumab treatment, indicating that this variant correlates with disease outcome independent of therapy. This supports the classification as prognostic evidence, as it relates to survival metrics.

Predictive, Prognostic evidence:

Predictive: PIK3CA mutations predicted for longer local recurrence-free survival, indicating a correlation with treatment response or disease outcome based on therapy context.

Prognostic: The study reports that patients with high S-phase fraction had longer recurrence-free survival if they carried mutations in the PIK3CA gene, suggesting that this variant correlates with disease outcome independent of therapy.

Prognostic, Oncogenic evidence:

Oncogenic: The abstract discusses somatic mutations of PIK3CA and their role in the pathogenesis and progression of human breast cancers, indicating that these mutations contribute to tumor development.

Prognostic: The study reports that PIK3CA mutations are significantly associated with a favorable prognosis, demonstrating that the mutation status serves as an independent prognostic factor.

Predictive evidence:

Predictive: The study validates HER2 amplification and PIK3CA mutation as biomarkers for sensitivity to the PI3K inhibitor GDC-0941, indicating a direct correlation between these variants and treatment response in breast cancer models.

Predictive evidence:

Predictive: The study discusses how increased activity of the PI3K pathway in cancer is associated with resistance to chemotherapeutic agents, suggesting that PI3K inhibitors like GDC-0941 could overcome this resistance and enhance the effectiveness of doxorubicin treatment. This indicates a correlation between the variant's activity and the response to therapy, fulfilling the criteria for predictive evidence.

Predictive evidence:

Predictive: The study demonstrates that GDC-0941 sensitizes breast cancer cells to ABT-737, indicating a correlation with enhanced response to therapy when these agents are combined. This suggests that the variant may influence treatment sensitivity, as the combination leads to increased cytotoxicity and apoptosis in breast cancer cells.

Predictive, Functional evidence:

Predictive: The study investigates the pharmacokinetics and activity of GDC-0941, a PI3K pathway inhibitor, in various mouse models, suggesting that the variant's interaction with P-glycoprotein and breast cancer resistance protein may influence treatment response in patients with brain tumors.

Functional: The research demonstrates that GDC-0941 is a substrate of P-glycoprotein and Bcrp1, indicating that the variant alters the molecular function of these transporters, which impacts the drug's brain penetration and pharmacokinetics.

Predictive evidence:

Predictive: The study evaluates the relationship between GDC-0941 plasma concentrations and tumor reduction, indicating that the variant's activation or transforming mutations in the PI3K pathway correlate with the response to this specific therapy. The mention of "tumor pharmacodynamic biomarker" responses and their association with antitumor efficacy further supports this classification.

Predictive evidence:

Predictive: The study discusses the resistance to HER2 inhibitors in breast cancer and investigates the combinatorial activity of GDC-0941, a PI3K inhibitor, with standard therapies, indicating that the variant's presence may correlate with treatment response. The results show that the combination of GDC-0941 with HER2-targeted therapies leads to significant growth inhibition, suggesting a predictive relationship between the variant and therapeutic efficacy.

Predictive evidence:

Predictive: The study discusses how trastuzumab treatment correlates with the disruption of HER2/HER3 interactions and leads to antiproliferative effects, indicating that the variant's presence may influence response to therapy. The mention of a selective PI3K inhibitor being effective in combination with trastuzumab further supports the predictive nature of the variant in relation to treatment response.

Oncogenic evidence:

Oncogenic: The abstract discusses that somatic mutations in the PIK3CA gene play a role in tumor initiation, indicating that these mutations contribute to tumor development in breast cancer. The mention of PIK3CA mutations being present in both in situ and invasive breast carcinomas supports the classification of this variant as oncogenic.

Diagnostic, Prognostic evidence:

Diagnostic: The study establishes that IDH1 mutations are a strong genetic marker for distinguishing between secondary glioblastomas and primary glioblastomas, indicating their role in defining and classifying these disease subtypes.

Prognostic: The results indicate that glioblastoma patients with IDH1 mutations have significantly longer survival compared to those without, suggesting that these mutations correlate with better disease outcomes independent of therapy.

nan evidence:

Missing abstract

Diagnostic, Prognostic, Oncogenic evidence:

Prognostic: The study reports that loss of heterozygosity (LOH) 10q is predictive of shorter survival, indicating a correlation between this genetic alteration and disease outcome independent of therapy. The observed survival rates at various time points further support the prognostic implications of the genetic alterations discussed.

Diagnostic: The abstract mentions the frequency of various genetic alterations in glioblastomas, including TP53 mutations, which are used to classify and define the disease subtypes. The association of these mutations with primary and secondary glioblastomas provides evidence for their role in disease classification.

Oncogenic: The presence of TP53 mutations and LOH 10q in glioblastomas suggests that these somatic variants contribute to tumor development and progression, particularly in the context of secondary glioblastomas. The study highlights the different mechanisms of mutation acquisition in these tumor subtypes, reinforcing the oncogenic nature of these alterations.

Prognostic evidence:

Prognostic: The study investigates the relationship between histologic factors and survival in glioblastoma patients, indicating that certain histologic features correlate with patient outcomes, particularly noting the strong negative relationship between advancing age and duration of postoperative survival. This suggests that the variant's presence or absence may influence prognosis independent of therapy.

Diagnostic, Prognostic, Oncogenic evidence:

Prognostic: The abstract discusses median survival times for various glioma types, indicating that the prognosis of diffusely infiltrating gliomas is poorer, with specific survival rates provided for different grades. This correlates the presence of certain genetic alterations, such as TP53 mutations and LOH 10q, with survival outcomes, thus providing prognostic evidence.

Diagnostic: The abstract mentions the frequency of TP53 mutations in different glioma subtypes, which can be used to classify or define these tumors. The association of specific mutations with certain tumor types supports the use of these variants as diagnostic markers.

Oncogenic: The abstract indicates that TP53 mutations and other genetic alterations are frequent in gliomas and discusses their association with tumor characteristics and survival, suggesting that these mutations contribute to tumor development or progression. This aligns with the definition of oncogenic evidence.

Diagnostic, Oncogenic evidence:

Diagnostic: The abstract discusses the distinct disease subtypes of glioblastoma, indicating that primary and secondary glioblastomas are characterized by different genetic pathways and mutation patterns. This classification of glioblastoma based on genetic alterations supports the use of these variants as diagnostic markers for defining and confirming disease subtypes.

Oncogenic: The abstract mentions that TP53 mutations are the most frequent and earliest detectable genetic alteration in the progression to secondary glioblastoma, suggesting that these mutations contribute to tumor development. This indicates that the somatic variants discussed are involved in oncogenic processes related to glioblastoma.

Predisposing, Functional evidence:

Predisposing: The abstract mentions "germline mutations that affect components of the Ras-Raf-MEK-ERK pathway," indicating that these inherited mutations confer risk for developmental disorders, which aligns with the definition of predisposing variants.

Functional: The abstract states that "many of these mutant alleles encode proteins with aberrant biochemical and functional properties," suggesting that the variants alter molecular or biochemical function, which supports the functional evidence type.

Oncogenic evidence:

Oncogenic: The study provides evidence that RAS oncogenes, specifically K- or NRAS genes activated by point mutation, contribute to tumor development in various types of lung carcinomas, indicating their role in oncogenesis. The detection of activated protooncogenes in the majority of lung tumor DNAs supports the conclusion that these variants are involved in tumor progression.

Oncogenic evidence:

Oncogenic: The abstract states that the N-Ras(G60E) variant, along with other Ras mutants, exhibited oncogenic properties in biochemical and functional assays, indicating its contribution to tumor development or progression.

Oncogenic evidence:

Oncogenic: The study discusses mutations in the N-ras gene found in patients with cutaneous melanoma, suggesting that these mutations contribute to tumor development, particularly in the context of UV exposure. The mention of mutations being localized at dipyrimidine sites known to be targets of UV damage further supports the notion of these mutations playing a role in tumor progression.

Predictive, Diagnostic, Oncogenic evidence:

Diagnostic: The study investigates the incidence of BRAF and NRAS mutations in various melanoma subtypes, indicating that these mutations are used to classify and define the molecular genetic profiles of different melanoma types, particularly in mucosal melanomas.

Predictive: The mention of "possible new therapeutic options of anti-RAF treatment" for patients with BRAF mutations suggests that these mutations may correlate with response to specific therapies, indicating a predictive relationship.

Oncogenic: The study discusses the unique oncogenetic pathways of tumor development in different melanoma subtypes, implying that BRAF mutations contribute to tumor development in the context of melanoma, which supports the classification as oncogenic.

Predictive, Diagnostic evidence:

Diagnostic: The study discusses the identification of deleterious mutations in moderate-risk breast and ovarian cancer genes and Lynch syndrome genes among patients lacking BRCA1/2 mutations, indicating that these mutations are associated with hereditary breast and/or ovarian cancer (HBOC). This suggests that the presence of these mutations can be used to classify and confirm the risk of disease in individuals, thus supporting their role as diagnostic markers.

Predictive: The findings indicate that the identification of non-BRCA1/2 mutations can lead to changes in clinical management and additional disease-specific screening or prevention measures, suggesting that these mutations correlate with the response to clinical interventions. This highlights the potential for these variants to influence treatment decisions based on their presence.

Diagnostic, Predisposing evidence:

Predisposing: The study discusses the identification of germline BRCA1/2 mutations and other pathogenic variants in genes associated with cancer risk, indicating that these variants confer inherited risk for developing cancer. The mention of "germline-DNA sequencing panel for cancer-risk assessment" supports this classification.

Diagnostic: The study evaluates the performance of a customized sequencing panel for cancer-risk assessment, which is used to identify and confirm pathogenic variants in patients, thereby classifying them based on their genetic mutations. The identification of variants in genes like ATM, BLM, and others suggests their role in defining disease risk.

Predictive, Oncogenic evidence:

Predictive: The study discusses a selective R132H-IDH1 inhibitor (AGI-5198) that blocks the ability of the mutant enzyme to produce R-2-hydroxyglutarate, indicating that the presence of the R132H variant correlates with the response to this specific therapy, as it impaired the growth of IDH1-mutant glioma cells.

Oncogenic: The abstract mentions that the mutant IDH1 (specifically the R132H variant) promotes glioma growth, suggesting that this somatic variant contributes to tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses the novel pan-mutant IDH1 inhibitor BAY1436032, which specifically inhibits R-2HG production and induces myeloid differentiation in AML cells carrying IDH1 mutations, including R132G. This indicates a correlation between the presence of the R132G variant and the response to the therapy.

Oncogenic: The abstract mentions that mutations in IDH1, including R132G, contribute to tumor development by leading to the production of the oncometabolite R-2HG, which promotes tumorigenesis through mechanisms such as histone and DNA hypermethylation. This supports the classification of R132G as an oncogenic variant.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses somatic gain-of-function mutations in IDH1 and IDH2, indicating that these mutations contribute to tumor development and progression by causing a block in cellular differentiation, which is characteristic of oncogenic behavior.

Predictive: The study highlights that the mutant IDH2 enzyme can be targeted by the inhibitor AG-221, which not only suppresses 2HG production but also induces cellular differentiation in IDH2 mutation-positive AML cells, suggesting a correlation with treatment response.

Predictive, Oncogenic evidence:

Predictive: The study discusses the development of BAY 1436032 as a pan-inhibitor targeting IDH1 mutations, including R132H and R132L, and highlights its ability to significantly prolong survival in mice with tumors carrying the IDH1R132H mutation, indicating a correlation with treatment response.

Oncogenic: The abstract mentions that mutations in codon 132 of IDH1, including R132H and R132L, are frequent in various tumors, suggesting that these somatic variants contribute to tumor development and progression through their neomorphic enzyme activity.

Predictive, Diagnostic evidence:

Predictive: The study demonstrates that IDH mutant (IDHm) intrahepatic cholangiocarcinoma (ICC) cells show a striking response to the multikinase inhibitor dasatinib, indicating a correlation between the IDH mutations and sensitivity to this specific therapy.

Diagnostic: The abstract states that IDH mutations define a distinct subtype of ICC, suggesting that these mutations are used to classify and identify this specific malignancy.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses the presence of the IDH1 mutation R132H in a patient with metastatic pancreatic ductal adenocarcinoma (PDA), indicating that this somatic variant is associated with tumor development in this specific cancer type. The mention of the mutation being detected through molecular profiling supports its role in oncogenesis.

Predictive: The abstract notes that the patient received a mutant IDH1 inhibitor (AG-120) as a treatment option, but there was no response. This indicates that the R132H variant was evaluated in the context of therapy, suggesting a predictive relationship regarding treatment response.

Predictive evidence:

Predictive: The study indicates that patients with non-small-cell lung cancer harboring EGFR mutations, including the L858R point mutation, respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib, suggesting a correlation between the presence of this variant and improved treatment outcomes. The results show that gefitinib leads to significantly longer progression-free survival compared to standard chemotherapy, highlighting the predictive nature of the L858R mutation in response to therapy.

Predictive evidence:

Predictive: The study indicates that depletion of Akt3 in triple-negative breast cancer (TNBC) sensitizes cells to the pan-Akt inhibitor GSK690693, suggesting that the variant correlates with sensitivity to a specific therapy. This implies a potential therapeutic target for treatment in TNBC, aligning with the predictive evidence type.

Predictive, Oncogenic evidence:

Predictive: The study discusses the resistance mechanisms to the AKT inhibitor MK2206, indicating that the expression of AKT3 in resistant cells correlates with a loss of sensitivity to this therapy. This suggests that AKT3 plays a role in the response to treatment, making it predictive of resistance to AKT inhibitors.

Oncogenic: The upregulation of AKT3 in AKT inhibitor-resistant breast cancer cells suggests that it contributes to tumor progression and resistance mechanisms, indicating its role as an oncogenic driver in this context.

Predictive, Diagnostic evidence:

Predictive: The study evaluates the efficacy of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung whose tumors demonstrated FGFR1 amplification, indicating that the variant correlates with response to a specific therapy. The mention of "overall response" and "disease control rate" further supports this classification as it directly relates to treatment outcomes.

Diagnostic: The study specifies that patients were enrolled based on their tumors demonstrating FGFR1 amplification of > 5 copies, which indicates that this variant is used to classify and confirm a specific subtype of lung cancer. This association with a defined characteristic of the disease supports the diagnostic classification.

Predictive, Oncogenic evidence:

Predictive: The study demonstrates that ATM-deficient MCL cell lines, such as Granta-519 and UPN2, are more sensitive to PARP-1 inhibition, indicating a correlation between the ATM variant status and response to therapy. Additionally, the use of the PARP-1 inhibitor olaparib significantly decreased tumor growth and increased overall survival in mice with ATM-deficient tumors, further supporting the predictive nature of this variant in therapeutic response.

Oncogenic: The characterization of ATM alterations in MCL and the observation that ATM-deficient cells exhibit defective DNA damage signaling and increased sensitivity to treatment suggest that these somatic variants contribute to tumor development and progression in this cancer type. The study's focus on the functional consequences of ATM mutations in the context of cancer supports the classification of these variants as oncogenic.

Oncogenic, Functional evidence:

Functional: The study describes how the CHEK2 mutation p.R474C alters the tertiary structure of the CHK2 protein by disrupting a salt bridge, indicating a change in molecular function. Additionally, the cell-based transfection analysis showed that this variant was unstable and scarcely activated, further supporting its functional impact.

Oncogenic: The conclusion that the homozygous CHEK2 variant p.R474C was contributory in the case of familial cancer suggests that this somatic variant may play a role in tumor development or progression, particularly given the context of multiple primary cancers in the patients.

Diagnostic evidence:

Diagnostic: The abstract discusses the updated recommendations for the diagnosis and management of acute myeloid leukemia (AML), which includes a revised version of the ELN genetic categories. This indicates that the variants are being used to classify or define the disease, aligning with the diagnostic evidence type.

Predictive, Functional evidence:

Predictive: The study indicates that the JAK1S703I mutation is sensitive to treatment with the JAK1/2 inhibitor, ruxolitinib, suggesting a correlation between this variant and therapeutic response. This is supported by the observation that the mutant PDX model showed sensitivity to the treatment, while other non-activating mutants did not.

Functional: The JAK1S703I mutation was shown to activate the JAK-STAT signaling pathway and drive cell proliferation in vitro, indicating that this variant alters molecular function. The introduction of this mutation into cell lines demonstrated its capability to enhance signaling in the absence of cytokine stimulation.

Predictive, Diagnostic evidence:

Predictive: The study assesses the ability of tumor genomic loss of heterozygosity (LOH) to predict response to rucaparib, indicating that LOH high status correlates with a better response to this PARP inhibitor in patients with ovarian carcinoma. This is supported by the findings that progression-free survival was significantly longer in the LOH high subgroup compared to the LOH low subgroup, demonstrating the predictive nature of the variant in relation to treatment outcomes.

Diagnostic: The classification of patients into homologous recombination deficiency subgroups based on tumor mutational analysis, including BRCA mutant and LOH high, indicates that these variants are used to define and classify the disease subtype. This classification is essential for determining the appropriate treatment strategy, thus supporting the diagnostic evidence type.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses the ability of the L858R mutation to predict sensitivity to gefitinib, stating that it has been examined for its predictive capabilities in the context of treatment response. The mention of patients with the L858R mutation who did not respond to gefitinib further emphasizes the predictive nature of this variant regarding treatment resistance.

Oncogenic: The L858R mutation is described as a common somatic mutation in the EGFR gene associated with non-small-cell lung cancer (NSCLC), indicating its role in tumor development or progression. The context of the mutation being part of the EGFR gene, which is known to drive cancer, supports its classification as oncogenic.

Predisposing, Oncogenic evidence:

Predisposing: The abstract mentions that DDX41 mutations are identified as both germline and acquired somatic mutations in families with multiple cases of hematologic malignancies, indicating that these mutations confer inherited risk for developing diseases like myelodysplastic syndrome and acute myeloid leukemia.

Oncogenic: The abstract suggests that DDX41 acts as a tumor suppressor and discusses the identification of mutations in families with hematologic malignancies, implying that these somatic mutations contribute to tumor development or progression.

nan evidence:

Missing abstract

nan evidence:

Missing abstract

Predisposing evidence:

Predisposing: The abstract states that the identified 700-kb tandem duplication at locus 14q32.13-q32.2 "increases the predisposition to myeloid malignancies," indicating that this variant is associated with an inherited risk for developing disease.

Predisposing, Oncogenic, Functional evidence:

Predisposing: The study describes a familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DDX41 gene, indicating that these mutations confer inherited risk for developing the disease.

Oncogenic: The abstract mentions that DDX41 is affected by somatic mutations in sporadic cases of myeloid neoplasms, suggesting that these mutations contribute to tumor development or progression.

Functional: The abstract states that DDX41 lesions caused altered pre-mRNA splicing and RNA processing, indicating that the variant affects molecular or biochemical function.

Oncogenic evidence:

Oncogenic: The variant N356fs is mentioned in the results section as a somatic mutation associated with T-ALL, indicating its contribution to tumor development or progression. The classification as "homo (LOH)" further supports its role in oncogenesis within the context of leukemia.

Diagnostic, Predisposing evidence:

Predisposing: The study discusses inherited mutations in ETV6, including the N385fs variant, which are associated with susceptibility to acute leukemia, indicating that these mutations confer inherited risk for developing the disease.

Diagnostic: The presence of the ETV6 N385fs mutation is used to classify and confirm the diagnosis of leukemia in the affected individuals, as it segregates with the disease in the studied kindreds.

Predisposing evidence:

Predisposing: The study discusses a "familial platelet disorder with propensity to myeloid malignancy," indicating that the germline heterozygous mutations in Runt-related transcription factor 1 confer inherited risk for developing myeloid malignancies. This aligns with the definition of a predisposing variant as it is explicitly described as germline and associated with an inherited condition.

Diagnostic, Functional evidence:

Diagnostic: The abstract mentions that "Platelet dysfunction suggestive of defective delta-granule release could be of values for the diagnosis of FPD/AML," indicating that the variant is used to define or confirm a disease, specifically in the context of autosomal dominant thrombocytopenia.

Functional: The results section describes various assays performed to investigate platelet function and delta-granule release, which implies that the variant affects molecular or biochemical functions related to platelet aggregation and granule release.

Diagnostic, Predisposing evidence:

Predisposing: The study discusses "inherited thrombocytopenias," indicating that the variants are germline and confer inherited risk for developing this disorder. The mention of "inherited or sustained thrombocytopenia of unknown etiology" supports the classification as predisposing.

Diagnostic: The identification of "pathogenic" or "likely pathogenic" variants in patients with thrombocytopenia suggests that these variants are used to confirm or classify the disease. The use of whole exome sequencing to elucidate potential pathogenic genetic variants further supports this classification.

Predisposing, Oncogenic evidence:

Predisposing: The abstract discusses "monoallelic RUNX1 germline mutations" found in families with familial platelet disorder (FPD), indicating that these inherited mutations confer a genetic predisposition to developing acute myeloid leukemia (AML).

Oncogenic: The identification of "a second RUNX1 alteration" in AML cases, including "acquired point mutations" and "duplication of the altered RUNX1 allele," suggests that these somatic changes contribute to tumor development and progression in the context of AML.

Diagnostic, Prognostic evidence:

Diagnostic: The study discusses GATA2 deficiency and its association with various diseases, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), indicating that the variant is used to classify and confirm these conditions. The identification of genotype-phenotype associations further supports its role as a diagnostic marker.

Prognostic: The abstract mentions that monocytopenia and lymphocytopenia correlate with the presence of disease, suggesting that the variant may have implications for disease outcomes independent of therapy. This correlation indicates a potential prognostic value of the GATA2 deficiency in predicting disease severity or progression.

Predisposing, Functional evidence:

Predisposing: The study identifies the p.Thr355del variant as a heritable mutation associated with familial myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), indicating that it confers inherited risk for developing these diseases.

Functional: The abstract mentions that the mutations, including p.Thr355del, affect transactivation of target genes, cellular differentiation, apoptosis, and global gene expression, demonstrating that this variant alters molecular or biochemical function.

Prognostic evidence:

Prognostic: The abstract indicates that KRAS G13D is associated with poor survival outcomes in mCRC patients, suggesting that this variant correlates with disease prognosis independent of therapy. The mention of "inferior PFS and OS" highlights its relevance in predicting patient outcomes.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The study discusses the patient's response to pembrolizumab, indicating that the hypermutated glioblastoma may be susceptible to checkpoint blockade therapy, which correlates with the variant's potential impact on treatment response. The mention of "an objective radiographic response" suggests a relationship between the variant and the effectiveness of the therapy.

Diagnostic: The abstract states that the patient has a "POLE germline alteration," which is used to define the hypermutated genotype of the glioblastoma, indicating that this variant is associated with a specific disease subtype. This classification supports the use of the variant as a biomarker for identifying patients with this particular tumor profile.

Oncogenic: The presence of a hypermutated genotype in the glioblastoma suggests that the variant contributes to tumor development or progression, as indicated by the tumor's characteristics and the context of the disease. The study implies that the POLE alteration plays a role in the tumor's aggressive behavior and its response to treatment.

Predictive, Diagnostic evidence:

Predictive: The study indicates that patients with TP53 mutations had a significantly higher response rate to decitabine therapy, with 100% of those with TP53 mutations achieving bone marrow blast clearance compared to only 41% of wild-type TP53 patients. This suggests that the presence of TP53 mutations correlates with a favorable clinical response to the treatment.

Diagnostic: The abstract mentions that TP53 mutations are associated with an unfavorable-risk cytogenetic profile, which is used to classify patients in terms of their risk for poor outcomes. This association supports the use of TP53 mutations as a biomarker for defining patient subtypes in AML and MDS.

Predictive, Oncogenic evidence:

Predictive: The study discusses how MET inhibitors suppressed tumor growth in xenograft models and reports a case where treatment with the targeted inhibitor crizotinib led to substantial tumor shrinkage, indicating a correlation between the MET fusion variant and response to therapy.

Oncogenic: The identification of MET fusions that activated MAPK signaling and induced aggressive glial tumors in vivo provides evidence that these somatic variants contribute to tumor development and progression in pediatric glioblastoma.

Predictive, Prognostic evidence:

Predictive: The study discusses TP53 and MDM2 alterations as being associated with cisplatin resistance, indicating that these variants may correlate with treatment response and resistance to chemotherapy. The mention of actionable alterations in cisplatin-resistant GCTs suggests potential sensitivity to targeted therapies, further supporting the predictive nature of these findings.

Prognostic: The abstract states that TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model, indicating that these variants correlate with inferior outcomes such as increased risk of cancer-related death. This suggests that the presence of these alterations can provide prognostic information regarding disease outcome.

Predictive, Oncogenic evidence:

Oncogenic: The L768S mutation is described as contributing to tumor development, as it exhibited a significant increase in tyrosine kinase-specific activity and promoted rapid growth in xenograft experiments. This indicates that the mutation plays a role in the oncogenic process within HER2-negative breast cancer.

Predictive: The study discusses how the L768S mutation affects sensitivity to HER2-targeted therapies, indicating that it may correlate with treatment response. Specifically, the presence of this mutation in HER2-negative tumors suggests a potential for these tumors to benefit from targeted therapies, highlighting its predictive nature regarding treatment outcomes.

Predictive, Oncogenic evidence:

Predictive: The study discusses the antitumor activity of dabrafenib plus trametinib specifically in patients with BRAF(V600E)-mutant NSCLC, indicating a correlation between the presence of this variant and the response to the therapy. The mention of "BRAF inhibition has shown antitumour activity" supports the predictive nature of the evidence regarding treatment response.

Oncogenic: The abstract states that BRAF mutations, including V600E, act as oncogenic drivers in non-small cell lung cancer, which indicates that these variants contribute to tumor development or progression. This classification is supported by the context of the study focusing on a specific mutation known to drive cancer.

Predictive, Diagnostic evidence:

Predictive: The study discusses how CDK12 deficiency serves as a clinically relevant biomarker of PARP1/2 inhibitor sensitivity, indicating that the presence of this variant correlates with response to therapy. The mention of "sensitivity to PARP1/2 inhibition" directly links the variant to treatment outcomes, fulfilling the criteria for predictive evidence.

Diagnostic: The identification of CDK12 as a biomarker of PARP1/2 inhibitor sensitivity suggests its role in classifying patients who may benefit from this specific therapy, thus providing diagnostic evidence. The abstract states that CDK12 is one of the genes significantly mutated in high-grade serous ovarian cancer, further supporting its use in defining a disease subtype.

Diagnostic evidence:

Diagnostic: The study identifies 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome, indicating that these deletions are used to classify and confirm the diagnosis of this genetic condition. The mention of the frequency of EPCAM deletions in confirmed Lynch syndrome families further supports its role as a diagnostic marker.

Predisposing evidence:

Predisposing: The abstract describes familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML) as an autosomal dominant disorder, indicating that the variant confers inherited risk for developing the disease. The mention of "haploinsufficiency of CBFA2" causing a congenital platelet defect and predisposing individuals to leukaemia further supports this classification.

Predictive, Prognostic evidence:

Prognostic: The abstract states that "the circulating concentrations of C-X-C motif chemokine ligand 10 (CXCL10), Fms-related tyrosine kinase 3 ligand (FLT3LG), interferon gamma (IFNG), and C-C motif chemokine ligand 4 (CCL4) were significantly associated with overall survival in both cohorts," indicating that these biomarkers correlate with disease outcome independent of therapy.

Predictive: The conclusion mentions that "High circulating levels of CXCL10 and FLT3LG predicted worse survival for patients with OS," suggesting that these biomarkers may correlate with treatment response or resistance, which aligns with predictive evidence.

nan evidence:

Missing abstract

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The abstract states that BRAF inhibitors are the standard treatment for metastatic melanoma with BRAF V600 mutations, indicating a correlation between the presence of this variant and the response to therapy. Additionally, the results highlight improved survival outcomes with BRAF inhibitors in patients with BRAF mutations, further supporting the predictive nature of this evidence.

Diagnostic: The abstract mentions that all patients had BRAFV600E mutations, which implies that this variant is used to classify and confirm the presence of a specific subtype of melanoma. This association with a specific disease subtype qualifies the evidence as diagnostic.

Oncogenic: The results section discusses the prevalence of BRAF mutations in malignant melanoma, specifically noting that the BRAF V600E mutation is the most common. This indicates that the variant contributes to tumor development or progression, supporting its classification as oncogenic.

Predictive evidence:

Predictive: The study discusses the correlation between isocitrate dehydrogenase 1/2 mutations and the response to venetoclax treatment, indicating that these mutations may serve as predictive markers of response consistent with BCL2 dependence. This suggests that the presence of these mutations could influence the effectiveness of the therapy in patients with AML.

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Diagnostic, Prognostic evidence:

Diagnostic: The presence of the T790M mutation is used to define a clinical subset of patients with acquired resistance to EGFR TKIs, indicating its role in classifying disease progression and prognosis.

Prognostic: The study reports that patients with the T790M mutation have a significantly longer postprogression survival compared to those without the mutation, suggesting that T790M correlates with a more favorable disease outcome.

Predictive, Oncogenic evidence:

Predictive: The study discusses the emergence of imatinib-resistant clones in patients with metastatic gastrointestinal stromal tumors (GIST) and correlates this with disease progression, indicating that the presence of specific mutations in the KIT and PDGFRA kinases is associated with resistance to imatinib therapy.

Oncogenic: The identification of new activating kinase mutations in 80% of patients with progressive disease suggests that these somatic variants contribute to tumor development or progression in the context of GISTs.

Oncogenic evidence:

Oncogenic: The study discusses clonal chromosome aberrations involving 2p23 and the rearrangement of the ALK gene, suggesting that these alterations contribute to the development of inflammatory myofibroblastic tumors (IMT). This indicates that the variant plays a role in tumor progression, aligning with the definition of oncogenic evidence.

Predictive, Prognostic evidence:

Predictive: The study discusses how mutation scoring based on in vitro inhibitory concentration of TKI-mutation pairs can predict long-term clinical outcomes, indicating that the T315I variant has a low sensitivity to treatment, which correlates with response rates to therapy.

Prognostic: The results indicate that tumors with low and intermediate mutation scores, including those with the T315I variant, had worse event-free and overall survival rates compared to those with highly sensitive mutations, demonstrating a correlation with disease outcome independent of therapy.

Predisposing, Oncogenic evidence:

Predisposing: The study identifies germline mutations in the ALK gene as the main cause of familial neuroblastoma, indicating that these inherited mutations confer a risk for developing the disease.

Oncogenic: The abstract mentions that somatically acquired mutations in the ALK gene were predicted to be oncogenic drivers, as they resulted in constitutive phosphorylation and were linked to tumor growth.

Predictive evidence:

Predictive: The abstract states that EGFR gene mutations, including G719X, predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). This indicates a correlation between the presence of the G719X variant and the effectiveness of specific therapies, qualifying it as predictive evidence.

Predictive, Diagnostic evidence:

Predictive: The study discusses the efficacy of trastuzumab-DM1 (T-DM1) in patients with HER2-positive metastatic breast cancer, indicating that the response rates were higher among patients with confirmed HER2-positive tumors. This suggests a correlation between the HER2 variant status and the response to the therapy, classifying it as predictive evidence.

Diagnostic: The abstract mentions that the response rates were higher among patients with confirmed HER2-positive tumors, which implies that the HER2 status is used to classify and confirm the disease subtype (HER2-positive metastatic breast cancer). This supports the classification as diagnostic evidence.

Diagnostic evidence:

Diagnostic: The abstract discusses the identification of individuals at increased risk of hereditary cancer syndromes and presents criteria for cancer genetic consultation referral, indicating that the variant is used to classify or confirm a disease or subtype. This aligns with the definition of the Diagnostic evidence type, as it involves the use of specific criteria to identify individuals who may harbor genetic variants associated with cancer risk.

Oncogenic evidence:

Oncogenic: The abstract discusses somatic mutations of EGFR that are associated with "oncogene addiction," indicating that these mutations contribute to tumor development or progression. The mention of "oncogenic shock" further supports the idea that these mutations play a critical role in the cancer's response to treatment, which is characteristic of oncogenic variants.

Predictive, Oncogenic evidence:

Oncogenic: The study identifies rearrangements of the RET proto-oncogene, specifically the CCDC6-RET fusion, as potential driver mutations in lung adenocarcinoma, indicating that this somatic variant contributes to tumor development and progression. The evidence is supported by the demonstration of the biological relevance of the CCDC6-RET gene products in promoting cell growth and survival.

Predictive: The study evaluates the efficacy of RET inhibitors, such as vandetanib, in reducing cell viability and demonstrates that treatment with these inhibitors can effectively target the CCDC6-RET fusion, suggesting a correlation with response to therapy. This indicates that the presence of the RET fusion may predict sensitivity to RET-targeted treatments.

Predictive, Diagnostic, Oncogenic evidence:

Oncogenic: The study identifies RET rearrangements as rare oncogenic alterations in non-small-cell lung cancer (NSCLC), indicating that these variants contribute to tumor development or progression.

Predictive: The results demonstrate that vandetanib, a tyrosine kinase inhibitor, shows clinical antitumor activity in patients with advanced RET-rearranged NSCLC, suggesting that the presence of RET rearrangements correlates with response to this specific therapy.

Diagnostic: The study defines RET rearrangement as a new molecular subgroup of NSCLC, indicating its role in classifying patients for targeted therapy, which aligns with the criteria for diagnostic evidence.

Predictive evidence:

Predictive: The study reports that the response rate of 33% with dabrafenib in patients with advanced BRAF V600E-mutant lung cancers indicates a correlation between the BRAF V600E variant and sensitivity to this specific therapy. This suggests that the presence of the BRAF V600E variant can predict treatment response to BRAF inhibitors.

Predictive evidence:

Predictive: The study discusses the efficacy of the CDK4/6 inhibitor ribociclib in combination with letrozole, indicating that this treatment correlates with improved progression-free survival in patients with HR-positive, HER2-negative advanced breast cancer. This suggests a predictive relationship between the variant (in this case, the treatment regimen) and the response to therapy.

Predictive, Prognostic evidence:

Predictive: The study discusses how the variant rs9637468 is associated with overall survival (OS) in patients treated with gemcitabine, indicating that it may help predict response to this therapy in pancreatic cancer. The mention of "gemcitabine response" directly links the variant to treatment outcomes, fulfilling the criteria for predictive evidence.

Prognostic: The results indicate that rs9637468 is associated with overall survival (OS) of patients treated with gemcitabine, which correlates with disease outcome independent of therapy. This association with OS suggests that the variant may have prognostic implications for patients undergoing treatment.

Prognostic, Predisposing evidence:

Predisposing: The study discusses "familial CEBPA mutations" and indicates that these mutations are "germ-line," which confers an inherited risk for developing acute myeloid leukemia (AML). This aligns with the definition of predisposing evidence as it highlights the genetic basis of the disease in affected families.

Prognostic: The abstract mentions a "cumulative incidence of relapse in familial AML was 56% at 10 years" and "long-term overall survival (10-year overall survival, 67%)," indicating that the presence of CEBPA mutations correlates with disease outcomes independent of therapy. This supports the classification as prognostic evidence.

Diagnostic, Oncogenic evidence:

Diagnostic: The abstract states that mutations occurring exclusively at arginine-625 in SF3B1 are associated with low-grade uveal melanomas, indicating that these mutations can be used to classify a distinct molecular subset of the disease.

Oncogenic: The results section describes the identification of deleterious somatic variants in SF3B1, specifically noting that the p.R625C alteration was found in multiple tumor samples, suggesting its role in tumor development or progression in uveal melanoma.

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Predictive, Oncogenic evidence:

Predictive: The study discusses how alterations in the mTOR pathway, specifically a nonsense mutation in TSC2, correlate with sensitivity to everolimus, indicating that this variant may predict treatment response. The mention of resistance developing in a patient after an 18-month response further emphasizes the predictive nature of the variant in relation to therapy outcomes.

Oncogenic: The identification of a mutation in TSC2 as a negative regulator of mTOR suggests that this somatic variant contributes to tumor development or progression, particularly in the context of anaplastic thyroid carcinoma. The study implies that the mutation plays a role in the tumor's response to treatment, reinforcing its oncogenic potential.

Predictive evidence:

Predictive: The abstract states that mutations in the Bcr-Abl kinase domain may cause resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients, indicating a correlation between the variant and treatment response. This suggests that the presence of specific mutations can influence the effectiveness of therapy, which aligns with the predictive evidence type.

Predictive evidence:

Predictive: The abstract discusses how NPM1 mutations in acute myeloid leukemia (AML) are associated with sensitivity to arsenic trioxide (ATO) and the beneficial effects of combining ATO with all-trans retinoic acid (ATRA) in treatment, indicating a correlation with treatment response. The statement about NPM1 mutant downregulation by ATO/ATRA potentiating response to daunorubicin further supports this classification.

Predictive, Oncogenic evidence:

Predictive: The study discusses the sensitivity of non-small-cell lung cancer (NSCLC) harboring the ALK rearrangement to the ALK inhibitor ceritinib, indicating a correlation between the presence of the ALK variant and the response to therapy. The overall response rate of 58% among patients treated with ceritinib further supports this predictive evidence regarding treatment efficacy.

Oncogenic: The mention of ALK rearrangement in NSCLC suggests that this somatic variant contributes to tumor development or progression, as it is associated with the cancer type being studied. The context of resistance mutations in ALK also implies its role in oncogenesis within the framework of the disease.

Predictive evidence:

Predictive: The study discusses the objective response rate (ORR) of alectinib in patients with crizotinib-refractory ALK-positive NSCLC, indicating that the variant (ALK rearrangement) correlates with treatment response to alectinib, a specific therapy. The mention of ORR and progression-free survival highlights the predictive nature of the variant in relation to therapy outcomes.