Q (sonnet): tell me about IDH1 mutations in glioma ▶ read_guide { "uri": "cbioportal://mutation-frequency-guide" } ▶ list_studies { "search": "glioma" } ◀ result # Mutation Frequency Analysis Guide ## IMPORTANT: Reporting Mutation Frequencies - **ALWAYS report frequencies as percentages**, not raw counts: `frequency = (altered_samples / total_profiled_samples) × 100` - For quick frequency lookups, **prefer the TCGA Pan-Cancer Atlas study first**, then offer to expand to other studies - When reporting across multiple studies, show **ranges** (e.g., "TP53 is mutated in 30–60% of samples") rather than a single average - **NEVER** sum mutation events across studies to compute an aggregate frequency — this can exceed 100% due to double-counting - Warn users that samples may overlap across cohorts (e.g., MSK studies may share patients) - **Choose and state the counting unit**: use patient-level frequencies for prevalence/rate questions unless the user explicitly asks for samples; use sample-level frequencies when the user asks about samples. - **For "across cancer types" questions**, jump to the [Cross-Cancer-Type Mutation Frequency](#cross-cancer-type-mutation-frequency) section below — there is one correct recipe and several common wrong ones. ## Counting Unit: Samples vs Patients Before answering any mutation count or frequency question, decide whether the unit is samples or patients and state that choice in the answer. | User wording | Counting unit | |--------------|---------------| | "prevalence", "rate", "fraction of patients", "patients with", "how common is" | Patient-level: `COUNT(DISTINCT patient_unique_id)` | | "samples", "specimens", "biopsies", sample-level cohort composition | Sample-level: `COUNT(DISTINCT sample_unique_id)` | | Ambiguous | Ask, or default to patient-level for prevalence/rate language and say so | ### Cross-study sample-count caveat When an answer touches more than one study and reports a sample count, prepend a one-line caveat: > Sample IDs are unique within cBioPortal study prefixes, not guaranteed biological-sample identifiers across studies; overlapping cohorts can count the same patient/sample more than once. Prefer one of these safer approaches: - Use a shipped `cancer_study_query_preferences` cohort such as `pan_cancer_tcga` or `all_studies_non_redundant`. - Restrict to one named study. - Aggregate by `patient_unique_id` when the biological question is patient prevalence. ## STOP rule: a frequency above 100% means your query is wrong If your query returns a frequency over 100%, **do not try to debug or explain the data inconsistency to the user**. The cause is always one of these query bugs: - Summing mutation events instead of `COUNT(DISTINCT sample_unique_id)` for the numerator - Using a study-wide sample count as the denominator instead of the gene-specific profiled count - Cross-study aggregation where the same biological sample appears under multiple `sample_unique_id` values (e.g., MSK-IMPACT and MSK-CHORD share patients) - **Joining the profiled CTE through `gene_panel` / `gene_panel_list` without a WES branch.** `gene_panel_id = 'WES'` is *not* a row in … (35166 more chars) ◀ result {"result":[{"cancer_study_identifier":"glioma_mskcc_2019","name":"Glioma (MSK, Clin Cancer Res 2019)","type_of_cancer_id":"difg","sample_count":1004,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=glioma_mskcc_2019"},{"cancer_study_identifier":"difg_glass","name":"Diffuse Glioma (GLASS Consortium)","type_of_cancer_id":"difg","sample_count":693,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=difg_glass"},{"cancer_study_identifier":"difg_tcga_gdc","name":"Diffuse Glioma (TCGA GDC, 2025)","type_of_cancer_id":"difg","sample_count":530,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=difg_tcga_gdc"},{"cancer_study_identifier":"lgg_tcga","name":"Brain Lower Grade Glioma (TCGA, Firehose Legacy)","type_of_cancer_id":"difg","sample_count":530,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lgg_tcga"},{"cancer_study_identifier":"lgg_tcga_pan_can_atlas_2018","name":"Brain Lower Grade Glioma (TCGA, PanCancer Atlas)","type_of_cancer_id":"difg","sample_count":514,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=lgg_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"difg_glass_2019","name":"Diffuse Glioma (GLASS Consortium, Nature 2019)","type_of_cancer_id":"difg","sample_count":444,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=difg_glass_2019"},{"cancer_study_identifier":"brain_cptac_2020","name":"Pediatric Brain Cancer (CPTAC/CHOP, Cell 2020)","type_of_cancer_id":"brain","sample_count":218,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=brain_cptac_2020"},{"cancer_study_identifier":"pcpg_tcga","name":"Pheochromocytoma and Paraganglioma (TCGA, Firehose Legacy)","type_of_cancer_id":"mnet","sample_count":184,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=pcpg_tcga"},{"cancer_study_identifier":"pcpg_tcga_pan_can_atlas_2018","name":"Pheochromocytoma and Paraganglioma (TCGA, PanCancer Atlas)","type_of_cancer_id":"soft_tissue","sample_count":178,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=pcpg_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"pcpg_tcga_pub","name":"Pheochromocytoma and Paraganglioma (TCGA, Cell 2017)","type_of_cancer_id":"soft_tissue","sample_count":178,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=pcpg_tcga_pub"},{"cancer_study_identifier":"hnsc_a5consortium_2025","name":"Hereditary SDHB-Mutant Pheochromocytomas and Paragangliomas (A5 Consortium, Nature Comm 2025)","type_of_cancer_id":"hnsc","sample_count":94,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hnsc_a5consortium_2025"},{"cancer_study_identifier":"glioma_msk_2018","name":"Glioma (MSK, Nature 2019)","type_of_cancer_id":"difg","sample_count":91,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=glioma_msk_2018"},{"cancer_study_identifier":"difg_msk_2023","name":"IDH-mutated Diffuse Glioma (MSK, Clin Cancer Res 2024)","type_of_cance … (855 more chars) ▶ clickhouse_run_select_query { "query": "SELECT * FROM gene_mutation_frequency_in_study(study = 'lgg_tcga_pan_can_atlas_2018', gene = 'IDH1')" } ◀ result {"rows":[{"cancer_type":"Glioma","altered_samples":395,"profiled_samples":514,"frequency_pct":76.8}]} ▶ clickhouse_run_select_query { "query": "SELECT * FROM gene_mutation_variants_in_study(study = 'lgg_tcga_pan_can_atlas_2018', gene = 'IDH1') ORDER BY altered_samples DESC LIMIT 15" } ◀ result {"rows":[{"mutation_variant":"R132H","mutation_type":"Missense_Mutation","altered_samples":358,"profiled_samples":514,"frequency_pct":69.6,"total_mutation_events":358},{"mutation_variant":"R132C","mutation_type":"Missense_Mutation","altered_samples":17,"profiled_samples":514,"frequency_pct":3.3,"total_mutation_events":17},{"mutation_variant":"R132G","mutation_type":"Missense_Mutation","altered_samples":11,"profiled_samples":514,"frequency_pct":2.1,"total_mutation_events":11},{"mutation_variant":"R132S","mutation_type":"Missense_Mutation","altered_samples":9,"profiled_samples":514,"frequency_pct":1.8,"total_mutation_events":9}]} ▶ list_studies { "search": "glioblastoma" } ▶ clickhouse_run_select_query { "query": "SELECT * FROM co_altered_genes_in_study(study = 'lgg_tcga_pan_can_atlas_2018', gene = 'IDH1', top_n = 15)" } ◀ result {"result":[{"cancer_study_identifier":"gbm_tcga","name":"Glioblastoma Multiforme (TCGA, Firehose Legacy)","type_of_cancer_id":"difg","sample_count":619,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga"},{"cancer_study_identifier":"gbm_tcga_gdc","name":"Glioblastoma Multiforme (TCGA GDC, 2025)","type_of_cancer_id":"difg","sample_count":611,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_gdc"},{"cancer_study_identifier":"gbm_tcga_pan_can_atlas_2018","name":"Glioblastoma Multiforme (TCGA, PanCancer Atlas)","type_of_cancer_id":"difg","sample_count":592,"has_guide":true,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"gbm_tcga_pub2013","name":"Glioblastoma (TCGA, Cell 2013)","type_of_cancer_id":"difg","sample_count":577,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_pub2013"},{"cancer_study_identifier":"gbm_tcga_pub","name":"Glioblastoma (TCGA, Nature 2008)","type_of_cancer_id":"difg","sample_count":206,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_tcga_pub"},{"cancer_study_identifier":"gbm_cptac_2021","name":"Glioblastoma (CPTAC, Cell 2021)","type_of_cancer_id":"difg","sample_count":99,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_cptac_2021"},{"cancer_study_identifier":"gbm_columbia_2019","name":"Glioblastoma (Columbia, Nat Med. 2019)","type_of_cancer_id":"difg","sample_count":42,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_columbia_2019"},{"cancer_study_identifier":"gbm_iatlas_prins_2019","name":"Glioblastoma (Randomized Clinical Trial, Nat Med. 2019) - iAtlas Harmonized","type_of_cancer_id":"adifg","sample_count":30,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=gbm_iatlas_prins_2019"}]} ◀ result {"rows":[{"hugo_gene_symbol":"TP53","mutant_altered":232,"mutant_profiled":395,"mutant_pct":58.7,"wildtype_altered":17,"wildtype_profiled":119,"wildtype_pct":14.3,"pct_difference":44.4},{"hugo_gene_symbol":"ATRX","mutant_altered":183,"mutant_profiled":395,"mutant_pct":46.3,"wildtype_altered":11,"wildtype_profiled":119,"wildtype_pct":9.2,"pct_difference":37.1},{"hugo_gene_symbol":"EGFR","mutant_altered":1,"mutant_profiled":395,"mutant_pct":0.3,"wildtype_altered":34,"wildtype_profiled":119,"wildtype_pct":28.6,"pct_difference":-28.3},{"hugo_gene_symbol":"IDH2","mutant_altered":0,"mutant_profiled":395,"mutant_pct":0,"wildtype_altered":21,"wildtype_profiled":119,"wildtype_pct":17.6,"pct_difference":-17.6},{"hugo_gene_symbol":"CIC","mutant_altered":99,"mutant_profiled":395,"mutant_pct":25.1,"wildtype_altered":9,"wildtype_profiled":119,"wildtype_pct":7.6,"pct_difference":17.5},{"hugo_gene_symbol":"PTEN","mutant_altered":3,"mutant_profiled":395,"mutant_pct":0.8,"wildtype_altered":21,"wildtype_profiled":119,"wildtype_pct":17.6,"pct_difference":-16.8},{"hugo_gene_symbol":"NF1","mutant_altered":9,"mutant_profiled":395,"mutant_pct":2.3,"wildtype_altered":22,"wildtype_profiled":119,"wildtype_pct":18.5,"pct_difference":-16.2},{"hugo_gene_symbol":"FUBP1","mutant_altered":45,"mutant_profiled":395,"mutant_pct":11.4,"wildtype_altered":3,"wildtype_profiled":119,"wildtype_pct":2.5,"pct_difference":8.9},{"hugo_gene_symbol":"NOTCH1","mutant_altered":36,"mutant_profiled":395,"mutant_pct":9.1,"wildtype_altered":2,"wildtype_profiled":119,"wildtype_pct":1.7,"pct_difference":7.4},{"hugo_gene_symbol":"FLG","mutant_altered":11,"mutant_profiled":395,"mutant_pct":2.8,"wildtype_altered":12,"wildtype_profiled":119,"wildtype_pct":10.1,"pct_difference":-7.3},{"hugo_gene_symbol":"PCLO","mutant_altered":9,"mutant_profiled":395,"mutant_pct":2.3,"wildtype_altered":9,"wildtype_profiled":119,"wildtype_pct":7.6,"pct_difference":-5.3},{"hugo_gene_symbol":"SMARCA4","mutant_altered":24,"mutant_profiled":395,"mutant_pct":6.1,"wildtype_altered":1,"wildtype_profiled":119,"wildtype_pct":0.8,"pct_difference":5.3},{"hugo_gene_symbol":"LRP2","mutant_altered":7,"mutant_profiled":395,"mutant_pct":1.8,"wildtype_altered":8,"wildtype_profiled":119,"wildtype_pct":6.7,"pct_difference":-4.9},{"hugo_gene_symbol":"COL6A3","mutant_altered":5,"mutant_profiled":395,"mutant_pct":1.3,"wildtype_altered":7,"wildtype_profiled":119,"wildtype_pct":5.9,"pct_difference":-4.6},{"hugo_gene_symbol":"ADGRV1","mutant_altered":7,"mutant_profiled":395,"mutant_pct":1.8,"wildtype_altered":7,"wildtype_profiled":119,"wildtype_pct":5.9,"pct_difference":-4.1}]} ▶ clickhouse_run_select_query { "query": "SELECT * FROM gene_mutation_frequency_in_study(study = 'gbm_tcga_pan_can_atlas_2018', gene = 'IDH1')" } ▶ resolve_and_route { "studyIds": [ "lgg_tcga_pan_can_atlas_2018", "gbm_tcga_pan_can_atlas_2018" ] } ◀ result {"rows":[{"cancer_type":"Glioblastoma","altered_samples":25,"profiled_samples":397,"frequency_pct":6.3}]} ◀ result {"success":true,"message":"Found 2 matching studies. Pick the best match (prefer TCGA → prefer PanCancer Atlas), use its metadata to call the appropriate navigation tool(s) and generate URLs immediately. Present other studies as alternatives.","data":{"totalCount":2,"studiesWithMetadata":[{"studyId":"lgg_tcga_pan_can_atlas_2018","name":"Brain Lower Grade Glioma (TCGA, PanCancer Atlas)","sampleCount":514,"studyViewUrl":"https://www.cbioportal.org/study?id=lgg_tcga_pan_can_atlas_2018","metadata":{"clinicalAttributeIds":["AGE","AJCC_PATHOLOGIC_TUMOR_STAGE","AJCC_STAGING_EDITION","ANEUPLOIDY_SCORE","BUFFA_HYPOXIA_SCORE","CANCER_TYPE","CANCER_TYPE_ACRONYM","CANCER_TYPE_DETAILED","DAYS_LAST_FOLLOWUP","DAYS_TO_BIRTH","DAYS_TO_INITIAL_PATHOLOGIC_DIAGNOSIS","DFS_MONTHS","DFS_STATUS","DSS_MONTHS","DSS_STATUS","ETHNICITY","FORM_COMPLETION_DATE","FRACTION_GENOME_ALTERED","GENETIC_ANCESTRY_LABEL","GRADE","HISTORY_NEOADJUVANT_TRTYN","ICD_10","ICD_O_3_HISTOLOGY","ICD_O_3_SITE","INFORMED_CONSENT_VERIFIED","IN_PANCANPATHWAYS_FREEZE","MSI_SCORE_MANTIS","MSI_SENSOR_SCORE","MUTATION_COUNT","NEW_TUMOR_EVENT_AFTER_INITIAL_TREATMENT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","OTHER_PATIENT_ID","PATH_M_STAGE","PATH_N_STAGE","PATH_T_STAGE","PERSON_NEOPLASM_CANCER_STATUS","PFS_MONTHS","PFS_STATUS","PRIMARY_LYMPH_NODE_PRESENTATION_ASSESSMENT","PRIOR_DX","RACE","RADIATION_THERAPY","RAGNUM_HYPOXIA_SCORE","SAMPLE_COUNT","SAMPLE_TYPE","SEX","SOMATIC_STATUS","SUBTYPE","TBL_SCORE","TISSUE_PROSPECTIVE_COLLECTION_INDICATOR","TISSUE_RETROSPECTIVE_COLLECTION_INDICATOR","TISSUE_SOURCE_SITE","TISSUE_SOURCE_SITE_CODE","TMB_NONSYNONYMOUS","TUMOR_TISSUE_SITE","TUMOR_TYPE","WEIGHT","WINTER_HYPOXIA_SCORE"],"molecularProfileIds":["lgg_tcga_pan_can_atlas_2018_gistic","lgg_tcga_pan_can_atlas_2018_log2CNA","lgg_tcga_pan_can_atlas_2018_mutations","lgg_tcga_pan_can_atlas_2018_rna_seq_v2_mrna","lgg_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","lgg_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","lgg_tcga_pan_can_atlas_2018_rppa","lgg_tcga_pan_can_atlas_2018_rppa_Zscores","lgg_tcga_pan_can_atlas_2018_structural_variants"],"genericAssayProfiles":["lgg_tcga_pan_can_atlas_2018_armlevel_cna","lgg_tcga_pan_can_atlas_2018_genetic_ancestry","lgg_tcga_pan_can_atlas_2018_methylation_hm27_hm450_merge","lgg_tcga_pan_can_atlas_2018_methylation_hm450"],"heatmapProfileIds":["lgg_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","lgg_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","lgg_tcga_pan_can_atlas_2018_rppa_Zscores"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations","mrna","protein","generic_assay_armlevel_cna","generic_assay_genetic_ancestry","generic_assay_methylation"]}},{"studyId":"gbm_tcga_pan_can_atlas_2018","name":"Glioblastoma Multiforme (TCGA, PanCancer Atlas)","sampleCount":592,"studyViewUrl":"https://www.cbioportal.org/study?id=gbm_tcga_pan_can_atlas_2018","metadata":{"clinicalAttributeIds":["AGE","AJCC_PATH … (2213 more chars) ▶ navigate_to_results_view { "studyIds": [ "lgg_tcga_pan_can_atlas_2018" ], "genes": [ "IDH1" ], "tab": "mutations" } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=lgg_tcga_pan_can_atlas_2018&gene_list=IDH1&case_set_id=lgg_tcga_pan_can_atlas_2018_all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=lgg_tcga_pan_can_atlas_2018&gene_list=IDH1&case_set_id=lgg_tcga_pan_can_atlas_2018_all","data":{"studyIds":["lgg_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"lgg_tcga_pan_can_atlas_2018","name":"Brain Lower Grade Glioma (TCGA, PanCancer Atlas)","sampleCount":514}],"genes":["IDH1"],"caseSetId":"lgg_tcga_pan_can_atlas_2018_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}} ▶ navigate_to_study_view { "studyIds": [ "lgg_tcga_pan_can_atlas_2018" ], "filterJson": { "geneFilters": [ { "molecularProfileIds": [ "lgg_tcga_pan_can_atlas_2018_mutations" ], "geneQueries": [ [ { "hugoGeneSymbol": "IDH1" } ] ] } ] } } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/study/summary?id=lgg_tcga_pan_can_atlas_2018#filterJson=%7B%22geneFilters%22%3A%5B%7B%22geneQueries%22%3A%5B%5B%7B%22hugoGeneSymbol%22%3A%22IDH1%22%7D%5D%5D%2C%22molecularProfileIds%22%3A%5B%22lgg_tcga_pan_can_atlas_2018_mutations%22%5D%7D%5D%7D","url":"https://www.cbioportal.org/study/summary?id=lgg_tcga_pan_can_atlas_2018#filterJson=%7B%22geneFilters%22%3A%5B%7B%22geneQueries%22%3A%5B%5B%7B%22hugoGeneSymbol%22%3A%22IDH1%22%7D%5D%5D%2C%22molecularProfileIds%22%3A%5B%22lgg_tcga_pan_can_atlas_2018_mutations%22%5D%7D%5D%7D","data":{"studyIds":["lgg_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"lgg_tcga_pan_can_atlas_2018","name":"Brain Lower Grade Glioma (TCGA, PanCancer Atlas)","sampleCount":514}],"tab":"summary","hasFilters":true,"hasPlotsConfig":false,"pageDescription":"Overview of all study data displayed as interactive charts summarizing available clinical and genomic data. Click within a chart to filter. Additional charts may be available in the Charts menu."}} ▶ navigate_to_results_view { "studyIds": [ "gbm_tcga_pan_can_atlas_2018" ], "genes": [ "IDH1" ], "tab": "mutations" } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=gbm_tcga_pan_can_atlas_2018&gene_list=IDH1&case_set_id=gbm_tcga_pan_can_atlas_2018_all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=gbm_tcga_pan_can_atlas_2018&gene_list=IDH1&case_set_id=gbm_tcga_pan_can_atlas_2018_all","data":{"studyIds":["gbm_tcga_pan_can_atlas_2018"],"studies":[{"studyId":"gbm_tcga_pan_can_atlas_2018","name":"Glioblastoma Multiforme (TCGA, PanCancer Atlas)","sampleCount":592}],"genes":["IDH1"],"caseSetId":"gbm_tcga_pan_can_atlas_2018_all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}} ═ answer (success) ### Direct links - **[IDH1 mutations lollipop plot — Lower Grade Glioma (LGG)](https://www.cbioportal.org/results/mutations?cancer_study_list=lgg_tcga_pan_can_atlas_2018&gene_list=IDH1&case_set_id=lgg_tcga_pan_can_atlas_2018_all)** — mutation positions, types, and R132H hotspot visualization across 514 samples. - **[LGG cohort filtered to IDH1-mutated samples](https://www.cbioportal.org/study/summary?id=lgg_tcga_pan_can_atlas_2018#filterJson=%7B%22geneFilters%22%3A%5B%7B%22geneQueries%22%3A%5B%5B%7B%22hugoGeneSymbol%22%3A%22IDH1%22%7D%5D%5D%2C%22molecularProfileIds%22%3A%5B%22lgg_tcga_pan_can_atlas_2018_mutations%22%5D%7D%5D%7D)** — explore clinical correlates (grade, subtype, survival) of IDH1-mutant cases. - **[IDH1 mutations lollipop plot — Glioblastoma (GBM)](https://www.cbioportal.org/results/mutations?cancer_study_list=gbm_tcga_pan_can_atlas_2018&gene_list=IDH1&case_set_id=gbm_tcga_pan_can_atlas_2018_all)** — the much smaller IDH1-mutant subset of GBM. If you'd like, I can also pull other glioma cohorts from the list above (e.g., the GLASS Consortium recurrence/longitudinal dataset, or the MSK IDH-mutant diffuse glioma study) or set up a formal survival/outcome comparison between IDH1-mutant and wild-type patients via the Group Comparison tool.