Q (haiku): In the TCGA Glioblastoma multiforme study (gbm_tcga_pan_can_atlas_2018), how many patients have an IDH1 R132H mutation and how many are IDH1 wild-type.

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

◀ 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)

▶ clickhouse_list_table_columns
{
 "table": "genomic_event_derived"
}

◀ result
{"columns":[{"name":"sample_unique_id","type":"String"},{"name":"hugo_gene_symbol","type":"String","comment":"HUGO gene symbol (e.g., TP53, KRAS, BRAF). Use for gene-specific queries."},{"name":"entrez_gene_id","type":"Int32"},{"name":"gene_panel_stable_id","type":"LowCardinality(String)"},{"name":"cancer_study_identifier","type":"LowCardinality(String)"},{"name":"genetic_profile_stable_id","type":"LowCardinality(String)"},{"name":"variant_type","type":"LowCardinality(String)","comment":"Type of genomic event: \"mutation\" for SNVs/indels, \"cna\" for copy number alterations, \"structural_variant\" for SVs. Always filter by this."},{"name":"mutation_variant","type":"String","comment":"Protein change notation (e.g., p.V600E, p.R175H). Use for specific variant queries. \"NA\" for non-mutation events."},{"name":"mutation_type","type":"LowCardinality(String)"},{"name":"mutation_status","type":"LowCardinality(String)","comment":"For mutations: Somatic, Germline, UNKNOWN, or UNCALLED. Filter mutation_status != \"UNCALLED\" to exclude uncertain calls. Include all other statuses."},{"name":"driver_filter","type":"LowCardinality(String)"},{"name":"driver_filter_annotation","type":"String"},{"name":"driver_tiers_filter","type":"LowCardinality(String)"},{"name":"driver_tiers_filter_annotation","type":"String"},{"name":"cna_alteration","type":"Nullable(Int8)","comment":"Copy number alteration: only 2 = amplification (AMP) and -2 = deep deletion (HOMDEL) are stored. Shallow deletion (-1), diploid (0) and gain (1) are not in this table; query genetic_alteration_derived WHERE profile_type = 'gistic' (alteration_value is a String, e.g. '-1'). NULL for non-CNA events."},{"name":"cna_cytoband","type":"String"},{"name":"sv_event_info","type":"String"},{"name":"patient_unique_id","type":"String"},{"name":"off_panel","type":"Bool","comment":"Boolean: 1 = mutation outside gene panel coverage (off-panel), 0 = within panel (on-panel). Filter off_panel = 0 for reliable frequency calculations."}]}

▶ list_studies
{
 "search": "gbm_tcga glioblastoma",
 "limit": 5
}

◀ 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"}]}

▶ clickhouse_run_select_query
{
 "query": "
SELECT *
FROM gene_mutation_variants_in_study(
    study = 'gbm_tcga_pan_can_atlas_2018',
    gene = 'IDH1'
)
ORDER BY altered_samples DESC
",
 "max_rows": 100
}

◀ result
{"rows":[{"mutation_variant":"R132H","mutation_type":"Missense_Mutation","altered_samples":22,"profiled_samples":397,"frequency_pct":5.5,"total_mutation_events":22},{"mutation_variant":"R132G","mutation_type":"Missense_Mutation","altered_samples":2,"profiled_samples":397,"frequency_pct":0.5,"total_mutation_events":2},{"mutation_variant":"R132C","mutation_type":"Missense_Mutation","altered_samples":1,"profiled_samples":397,"frequency_pct":0.3,"total_mutation_events":1}]}

▶ clickhouse_run_select_query
{
 "query": "
-- Get the number of profiled patients for IDH1
WITH profiled_patients AS (
    SELECT DISTINCT c.patient_unique_id
    FROM sample_to_gene_panel_derived s
    JOIN clinical_data_derived c USING (sample_unique_id)
    WHERE s.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
      AND s.alteration_type = 'MUTATION_EXTENDED'
      AND c.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
),
mutated_patients AS (
    SELECT DISTINCT c.patient_unique_id
    FROM genomic_event_derived g
    JOIN clinical_data_derived c USING (sample_unique_id)
    WHERE g.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
      AND g.hugo_gene_symbol = 'IDH1'
      AND g.variant_type = 'mutation'
      AND g.mutation_status != 'UNCALLED'
      AND g.off_panel = 0
      AND c.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
)
SELECT 
    (SELECT COUNT(*) FROM profiled_patients) AS total_profiled_patients,
    (SELECT COUNT(*) FROM mutated_patients) AS total_mutated_patients,
    (SELECT COUNT(*) FROM profiled_patients) - (SELECT COUNT(*) FROM mutated_patients) AS wildtype_patients
",
 "max_rows": 10
}

◀ result
{"rows":[{"total_profiled_patients":390,"total_mutated_patients":24,"wildtype_patients":366}]}

▶ clickhouse_run_select_query
{
 "query": "
-- Get patients with IDH1 R132H specifically
WITH profiled_patients AS (
    SELECT DISTINCT c.patient_unique_id
    FROM sample_to_gene_panel_derived s
    JOIN clinical_data_derived c USING (sample_unique_id)
    WHERE s.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
      AND s.alteration_type = 'MUTATION_EXTENDED'
      AND c.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
),
r132h_patients AS (
    SELECT DISTINCT c.patient_unique_id
    FROM genomic_event_derived g
    JOIN clinical_data_derived c USING (sample_unique_id)
    WHERE g.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
      AND g.hugo_gene_symbol = 'IDH1'
      AND g.mutation_variant = 'R132H'
      AND g.variant_type = 'mutation'
      AND g.mutation_status != 'UNCALLED'
      AND g.off_panel = 0
      AND c.cancer_study_identifier = 'gbm_tcga_pan_can_atlas_2018'
)
SELECT 
    'IDH1 R132H' AS mutation,
    (SELECT COUNT(*) FROM r132h_patients) AS patients_with_mutation,
    (SELECT COUNT(*) FROM profiled_patients) AS total_profiled_patients,
    ROUND((SELECT COUNT(*) FROM r132h_patients) * 100.0 / (SELECT COUNT(*) FROM profiled_patients), 1) AS frequency_pct
",
 "max_rows": 10
}

◀ result
{"rows":[{"mutation":"IDH1 R132H","patients_with_mutation":22,"total_profiled_patients":390,"frequency_pct":5.6}]}

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

◀ result
{"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"studiesWithMetadata":[{"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_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":["gbm_tcga_pan_can_atlas_2018_gistic","gbm_tcga_pan_can_atlas_2018_log2CNA","gbm_tcga_pan_can_atlas_2018_mutations","gbm_tcga_pan_can_atlas_2018_rna_seq_v2_mrna","gbm_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","gbm_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","gbm_tcga_pan_can_atlas_2018_rppa","gbm_tcga_pan_can_atlas_2018_rppa_Zscores","gbm_tcga_pan_can_atlas_2018_structural_variants"],"genericAssayProfiles":["gbm_tcga_pan_can_atlas_2018_armlevel_cna","gbm_tcga_pan_can_atlas_2018_genetic_ancestry","gbm_tcga_pan_can_atlas_2018_methylation_hm27_hm450_merge","gbm_tcga_pan_can_atlas_2018_methylation_hm450"],"heatmapProfileIds":["gbm_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","gbm_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","gbm_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"]}}]}}

▶ 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)
## Results

In the **TCGA Glioblastoma multiforme PanCancer Atlas** study (`gbm_tcga_pan_can_atlas_2018`), here are the IDH1 mutation status across **390 profiled patients**:

### IDH1 R132H Mutations
- **22 patients** with IDH1 R132H (5.6%)

### IDH1 Wild-Type
- **366 patients** without IDH1 mutations (93.8%)

### Additional IDH1 Variants
The study also contains:
- **2 patients** with IDH1 R132G (0.5%)
- **1 patient** with IDH1 R132C (0.3%)

This means **24 patients total** (6.2%) carry any IDH1 mutation, while **366 patients** (93.8%) are wild-type for IDH1. The R132H variant is by far the most common IDH1 mutation in this GBM cohort, consistent with its known prevalence as a defining mutation in IDH-mutant gliomas.

**[View IDH1 mutation details in cBioPortal](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)** — Interactive mutations table and lollipop plot.