Q (sonnet): tell me about IDH1 mutations in glioma

▶ read_guide
{
 "uri": "cbioportal://mutation-frequency-guide"
}

▶ search_oncotree
{
 "search_term": "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)

▶ list_studies
{
 "search": "glioma"
}

◀ result
{"result":[{"code":"AGNG","name":"Anaplastic Ganglioglioma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > AGNG"},{"code":"APXA","name":"Anaplastic Pleomorphic Xanthoastrocytoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > APXA"},{"code":"ASTR","name":"Astrocytoma, IDH-Mutant","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > ADIFG > ASTR","replacedCodes":["AASTR"]},{"code":"DASTR","name":"Diffuse Astrocytoma, MYB- or MYBL1-Altered","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > PDIFLG > DASTR"},{"code":"DIFG","name":"Diffuse Glioma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG"},{"code":"DNT","name":"Dysembryoplastic Neuroepithelial Tumor","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > DNT"},{"code":"ENCG","name":"Encapsulated Glioma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG"},{"code":"EPM","name":"Ependymoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > EPMT > EPM"},{"code":"GB","name":"Glioblastoma, IDH-Wildtype","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > ADIFG > GB","replacedCodes":["GBM"]},{"code":"GNC","name":"Gangliocytoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > GNC"},{"code":"GNG","name":"Ganglioglioma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > GNG"},{"code":"GNOS","name":"Glioma, NOS","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > GNOS","replacedCodes":["AOAST","OAST"]},{"code":"GSARC","name":"Gliosarcoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > ADIFG > GB > GSARC"},{"code":"HGGNOS","name":"High-Grade Glioma, NOS","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > HGGNOS"},{"code":"LGGNOS","name":"Low-Grade Glioma, NOS","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > LGGNOS"},{"code":"ODG","name":"Oligodendroglioma, IDH-mutant, and 1p/19q-Codeleted","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > ADIFG > ODG","replacedCodes":["AODG"]},{"code":"PAST","name":"Pilocytic Astrocytoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > PAST"},{"code":"PMA","name":"Pilomyxoid Astrocytoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > PMA"},{"code":"PXA","name":"Pleomorphic Xanthoastrocytoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > ENCG > PXA"},{"code":"SCGBM","name":"Small Cell Glioblastoma","score":65,"mainType":"Glioma","tissue":"CNS/Brain","hierarchy":"BRAIN > DIFG > ADIFG > GB > SCGBM"},{"code":"ADIFG","name":"Adult-Type Diffuse Glioma","score":50,"mainType":"Gliomas, Glioneuronal Tumors, and Neuronal Tumors","t … (782 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"
}

▶ list_studies
{
 "search": "glioblastoma"
}

◀ 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}]}

◀ 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"}]}

▶ clickhouse_run_select_query
{
 "query": "SELECT * FROM gene_mutation_frequency_in_study(study = 'gbm_tcga_pan_can_atlas_2018', gene = 'IDH1')"
}

◀ result
{"rows":[{"cancer_type":"Glioblastoma","altered_samples":25,"profiled_samples":397,"frequency_pct":6.3}]}

▶ resolve_and_route
{
 "studyIds": [
  "lgg_tcga_pan_can_atlas_2018",
  "gbm_tcga_pan_can_atlas_2018"
 ]
}

◀ 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_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)
[IDH1 mutations — Lower Grade Glioma, TCGA PanCancer Atlas](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) (514 samples)
[IDH1 mutations — Glioblastoma Multiforme, TCGA PanCancer Atlas](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) (592 samples)

Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes.

Other glioma cohorts of interest if you'd like to explore further: `difg_msk_2023` (IDH-mutated Diffuse Glioma, MSK), `glioma_mskcc_2019`, and `difg_glass` (GLASS Consortium, tracks IDH-mutant tumors longitudinally at recurrence).