Q (sonnet-5.5): show me cholangio with idh1 mutations other than r132

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

▶ search_oncotree
{
 "search_term": "cholangiocarcinoma"
}

▶ list_studies
{
 "search": "cholangio"
}

◀ 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 … (36467 more chars)

◀ result
{"result":[{"code":"CHOL","name":"Cholangiocarcinoma","score":80,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL"},{"code":"EHCH","name":"Extrahepatic Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL > EHCH"},{"code":"HCCIHCH","name":"Hepatocellular Carcinoma plus Intrahepatic Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Liver","hierarchy":"LIVER > HCCIHCH"},{"code":"IHCH","name":"Intrahepatic Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL > IHCH"},{"code":"PHCH","name":"Perihilar Cholangiocarcinoma","score":50,"mainType":"Hepatobiliary Cancer","tissue":"Biliary Tract","hierarchy":"BILIARY_TRACT > IPN > CHOL > PHCH"}]}

◀ result
{"result":[{"cancer_study_identifier":"chol_icgc_2017","name":"Cholangiocarcinoma (ICGC, Cancer Discov 2017)","type_of_cancer_id":"chol","sample_count":489,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_icgc_2017"},{"cancer_study_identifier":"ihch_msk_2021","name":"Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)","type_of_cancer_id":"ihch","sample_count":412,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_msk_2021"},{"cancer_study_identifier":"ihch_mskcc_2020","name":"Intrahepatic Cholangiocarcinoma (MSK, Clin Cancer Res 2021)","type_of_cancer_id":"ihch","sample_count":219,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_mskcc_2020"},{"cancer_study_identifier":"chol_msk_2018","name":"Cholangiocarcinoma (MSK, Clin Cancer Res 2018)","type_of_cancer_id":"chol","sample_count":195,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_msk_2018"},{"cancer_study_identifier":"hccihch_pku_2019","name":"Combined Hepatocellular and Intrahepatic Cholangiocarcinoma (Peking University, Cancer Cell 2019)","type_of_cancer_id":"hccihch","sample_count":173,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=hccihch_pku_2019"},{"cancer_study_identifier":"ihch_smmu_2014","name":"Intrahepatic Cholangiocarcinoma (Shanghai, Nat Commun 2014)","type_of_cancer_id":"ihch","sample_count":103,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_smmu_2014"},{"cancer_study_identifier":"chol_tcga_gdc","name":"Cholangiocarcinoma (TCGA GDC, 2025)","type_of_cancer_id":"chol","sample_count":51,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_tcga_gdc"},{"cancer_study_identifier":"chol_tcga","name":"Cholangiocarcinoma (TCGA, Firehose Legacy)","type_of_cancer_id":"chol","sample_count":51,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_tcga"},{"cancer_study_identifier":"chol_jhu_2013","name":"Intrahepatic Cholangiocarcinoma (JHU, Nat Genet 2013)","type_of_cancer_id":"chol","sample_count":40,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_jhu_2013"},{"cancer_study_identifier":"chol_tcga_pan_can_atlas_2018","name":"Cholangiocarcinoma (TCGA, PanCancer Atlas)","type_of_cancer_id":"chol","sample_count":36,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_tcga_pan_can_atlas_2018"},{"cancer_study_identifier":"chol_nccs_2013","name":"Cholangiocarcinoma (National Cancer Centre of Singapore, Nat Genet 2013)","type_of_cancer_id":"chol","sample_count":15,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=chol_nccs_2013"},{"cancer_study_identifier":"ihch_ismms_2015","name":"Intrahepatic Cholangiocarcinoma (Mount Sinai 2015)","type_of_cancer_id":"ihch","sample_count":8,"has_guide":false,"url":"https://www.cbioportal.org/study/summary?id=ihch_ismms_2015"},{"cancer_study_identifier":"chol_nus_2012","name":"Cholangiocarcinoma (National Universit … (163 more chars)

▶ clickhouse_run_select_query
{
 "query": "SELECT cancer_study_identifier, mutation_variant, mutation_type, count(DISTINCT sample_unique_id) AS samples, count(DISTINCT patient_unique_id) AS patients
FROM genomic_event_derived
WHERE variant_type='mutation' AND mutation_status != 'UNCALLED' AND hugo_gene_symbol='IDH1'
AND cancer_study_identifier IN ('chol_icgc_2017','ihch_msk_2021','ihch_mskcc_2020','chol_msk_2018','hccihch_pku_2019','ihch_smmu_2014','chol_tcga_gdc','chol_tcga','chol_jhu_2013','chol_tcga_pan_can_atlas_2018','chol_nccs_2013','ihch_ismms_2015','chol_nus_2012')
AND NOT startsWith(mutation_variant,'R132')
GROUP BY cancer_study_identifier, mutation_variant, mutation_type
ORDER BY cancer_study_identifier, samples DESC"
}

◀ result
{"rows":[{"cancer_study_identifier":"chol_tcga_gdc","mutation_variant":"G123E","mutation_type":"Missense_Mutation","samples":1,"patients":1},{"cancer_study_identifier":"hccihch_pku_2019","mutation_variant":"A268S","mutation_type":"Missense_Mutation","samples":1,"patients":1},{"cancer_study_identifier":"ihch_msk_2021","mutation_variant":"N349S","mutation_type":"Missense_Mutation","samples":1,"patients":1}]}

▶ clickhouse_run_select_query
{
 "query": "SELECT cancer_study_identifier, sample_unique_id, patient_unique_id, mutation_variant, mutation_type
FROM genomic_event_derived
WHERE variant_type='mutation' AND mutation_status != 'UNCALLED' AND hugo_gene_symbol='IDH1'
AND cancer_study_identifier IN ('chol_tcga_gdc','hccihch_pku_2019','ihch_msk_2021')
AND NOT startsWith(mutation_variant,'R132')"
}

▶ resolve_and_route
{
 "studyIds": [
  "chol_icgc_2017",
  "ihch_msk_2021",
  "ihch_mskcc_2020",
  "chol_msk_2018",
  "hccihch_pku_2019",
  "ihch_smmu_2014",
  "chol_tcga_gdc",
  "chol_tcga",
  "chol_jhu_2013",
  "chol_tcga_pan_can_atlas_2018",
  "chol_nccs_2013",
  "ihch_ismms_2015",
  "chol_nus_2012"
 ]
}

◀ result
{"rows":[{"cancer_study_identifier":"ihch_msk_2021","sample_unique_id":"ihch_msk_2021_P-0011223-T01-IM5","patient_unique_id":"ihch_msk_2021_P-0011223","mutation_variant":"N349S","mutation_type":"Missense_Mutation"},{"cancer_study_identifier":"chol_tcga_gdc","sample_unique_id":"chol_tcga_gdc_TCGA-ZH-A8Y7-01","patient_unique_id":"chol_tcga_gdc_TCGA-ZH-A8Y7","mutation_variant":"G123E","mutation_type":"Missense_Mutation"},{"cancer_study_identifier":"hccihch_pku_2019","sample_unique_id":"hccihch_pku_2019_Mix_23T","patient_unique_id":"hccihch_pku_2019_Mix_23","mutation_variant":"A268S","mutation_type":"Missense_Mutation"}]}

◀ result
{"success":true,"message":"Found 13 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":13,"studiesWithMetadata":[{"studyId":"chol_icgc_2017","name":"Cholangiocarcinoma (ICGC, Cancer Discov 2017)","sampleCount":489,"studyViewUrl":"https://www.cbioportal.org/study?id=chol_icgc_2017","metadata":{"clinicalAttributeIds":["AGE_AT_SURGERY","ANATOMICAL_SUBTYPE","CANCER_TYPE","CANCER_TYPE_DETAILED","ETHNICITY","HBV","HCV","HISTOLOGY","LIVER_FLUKE_STATUS","MUTATION_COUNT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PSC","SAMPLE_COUNT","SEX","STAGE","TARGETED_SEQ","TMB_NONSYNONYMOUS","TNM_STAGE","WHOLE_EXOME_SEQUENCING","WHOLE_GENOME_SEQUENCING"],"molecularProfileIds":["chol_icgc_2017_mutations"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}},{"studyId":"ihch_msk_2021","name":"Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)","sampleCount":412,"studyViewUrl":"https://www.cbioportal.org/study?id=ihch_msk_2021","metadata":{"clinicalAttributeIds":["ADJUVANT_CHEMO","AGE","BMI","CA19","CA19_HIGH","CANCER_TYPE","CANCER_TYPE_DETAILED","CHRONIC_HEPATITIS_ANY_TYPE","CIRRHOSIS","CLIN_PSC","DIABETES_STATUS","DUCT_TYPE","DZ_EXTENT","ECOG_BIN","FRACTION_GENOME_ALTERED","HAIC","HEP_B","HEP_C","LVI","MUTATION_COUNT","NEOADJ_CHEMO","ONCOTREE_CODE","OS_MONTHS","OS_MONTHS_FROM_RX","OS_STATUS","PD_INF","PNI","POSITIVE_LYMPH_NODE","POSITIVE_MARGIN","RFS_MONTHS","RFS_STATUS","SAMPLE_COUNT","SEX","SMOKING_STATUS","STEATOSIS","SYSTEMIC_CHEMO","TMB_NONSYNONYMOUS","TREATMENT_GROUP","TUMOR_GRADE","TUMOR_SIZE"],"molecularProfileIds":["ihch_msk_2021_cna","ihch_msk_2021_mutations","ihch_msk_2021_structural_variants"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations"]}},{"studyId":"ihch_mskcc_2020","name":"Intrahepatic Cholangiocarcinoma (MSK, Clin Cancer Res 2021)","sampleCount":219,"studyViewUrl":"https://www.cbioportal.org/study?id=ihch_mskcc_2020","metadata":{"clinicalAttributeIds":["AGE_AT_SEQ_REPORT","CANCER_TYPE","CANCER_TYPE_DETAILED","GENE_PANEL","INSTITUTE","METASTATIC_SITE","MSI_COMMENT","MSI_SCORE","MSI_TYPE","MUTATION_COUNT","ONCOTREE_CODE","PRIMARY_SITE","PROJECT_CODE","SAMPLE_COUNT","SAMPLE_COVERAGE","SOMATIC_STATUS","TMB_NONSYNONYMOUS","TUMOR_PURITY"],"molecularProfileIds":["ihch_mskcc_2020_cna","ihch_mskcc_2020_mutations","ihch_mskcc_2020_structural_variants"],"availableComparisonTabs":["overlap","clinical","alterations","mutations"]}},{"studyId":"chol_msk_2018","name":"Cholangiocarcinoma (MSK, Clin Cancer Res 2018)","sampleCount":195,"studyViewUrl":"https://www.cbioportal.org/study?id=chol_msk_2018","metadata":{"clinicalAttributeIds":["AGE","AGE_AT_SEQ_REPORT","AGE_CURRENT","CANCER_TYPE","CANCER_TYPE_DETAILED","ETHNICITY","FRACTION_GENOME_ALTERED","GENE_PANEL","INSTITUTE","METASTATIC_SITE","MSI_COMMENT","MSI_SCORE", … (11805 more chars)

▶ navigate_to_results_view
{
 "studyIds": [
  "chol_icgc_2017",
  "ihch_msk_2021",
  "ihch_mskcc_2020",
  "chol_msk_2018",
  "hccihch_pku_2019",
  "ihch_smmu_2014",
  "chol_tcga_gdc",
  "chol_tcga",
  "chol_jhu_2013",
  "chol_tcga_pan_can_atlas_2018",
  "chol_nccs_2013",
  "ihch_ismms_2015",
  "chol_nus_2012"
 ],
 "genes": [
  "IDH1: MUT != R132"
 ],
 "tab": "mutations"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=chol_icgc_2017%2Cihch_msk_2021%2Cihch_mskcc_2020%2Cchol_msk_2018%2Chccihch_pku_2019%2Cihch_smmu_2014%2Cchol_tcga_gdc%2Cchol_tcga%2Cchol_jhu_2013%2Cchol_tcga_pan_can_atlas_2018%2Cchol_nccs_2013%2Cihch_ismms_2015%2Cchol_nus_2012&gene_list=IDH1%3A+MUT+%21%3D+R132&case_set_id=all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=chol_icgc_2017%2Cihch_msk_2021%2Cihch_mskcc_2020%2Cchol_msk_2018%2Chccihch_pku_2019%2Cihch_smmu_2014%2Cchol_tcga_gdc%2Cchol_tcga%2Cchol_jhu_2013%2Cchol_tcga_pan_can_atlas_2018%2Cchol_nccs_2013%2Cihch_ismms_2015%2Cchol_nus_2012&gene_list=IDH1%3A+MUT+%21%3D+R132&case_set_id=all","data":{"studyIds":["chol_icgc_2017","ihch_msk_2021","ihch_mskcc_2020","chol_msk_2018","hccihch_pku_2019","ihch_smmu_2014","chol_tcga_gdc","chol_tcga","chol_jhu_2013","chol_tcga_pan_can_atlas_2018","chol_nccs_2013","ihch_ismms_2015","chol_nus_2012"],"studies":[{"studyId":"chol_icgc_2017","name":"Cholangiocarcinoma (ICGC, Cancer Discov 2017)","sampleCount":489},{"studyId":"ihch_msk_2021","name":"Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)","sampleCount":412},{"studyId":"ihch_mskcc_2020","name":"Intrahepatic Cholangiocarcinoma (MSK, Clin Cancer Res 2021)","sampleCount":219},{"studyId":"chol_msk_2018","name":"Cholangiocarcinoma (MSK, Clin Cancer Res 2018)","sampleCount":195},{"studyId":"hccihch_pku_2019","name":"Combined Hepatocellular and Intrahepatic Cholangiocarcinoma (Peking University, Cancer Cell 2019)","sampleCount":173},{"studyId":"ihch_smmu_2014","name":"Intrahepatic Cholangiocarcinoma (Shanghai, Nat Commun 2014)","sampleCount":103},{"studyId":"chol_tcga_gdc","name":"Cholangiocarcinoma (TCGA GDC, 2025)","sampleCount":51},{"studyId":"chol_tcga","name":"Cholangiocarcinoma (TCGA, Firehose Legacy)","sampleCount":51},{"studyId":"chol_jhu_2013","name":"Intrahepatic Cholangiocarcinoma (JHU, Nat Genet 2013)","sampleCount":40},{"studyId":"chol_tcga_pan_can_atlas_2018","name":"Cholangiocarcinoma (TCGA, PanCancer Atlas)","sampleCount":36},{"studyId":"chol_nccs_2013","name":"Cholangiocarcinoma (National Cancer Centre of Singapore, Nat Genet 2013)","sampleCount":15},{"studyId":"ihch_ismms_2015","name":"Intrahepatic Cholangiocarcinoma (Mount Sinai 2015)","sampleCount":8},{"studyId":"chol_nus_2012","name":"Cholangiocarcinoma (National University of Singapore, Nat Genet 2012)","sampleCount":8}],"genes":["IDH1"],"caseSetId":"all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}

═ answer (success)
I searched all 13 cholangiocarcinoma studies in cBioPortal for somatic IDH1 mutations at any position other than R132. Only 3 patients (3 samples) have one.

| Study | Patient | Sample | IDH1 change | Type |
|---|---|---|---|---|
| [Intrahepatic Cholangiocarcinoma (MSK, Hepatology 2021)](https://www.cbioportal.org/study/summary?id=ihch_msk_2021) | P-0011223 | P-0011223-T01-IM5 | N349S | Missense |
| [Cholangiocarcinoma (TCGA GDC, 2025)](https://www.cbioportal.org/study/summary?id=chol_tcga_gdc) | TCGA-ZH-A8Y7 | TCGA-ZH-A8Y7-01 | G123E | Missense |
| [Combined Hepatocellular and Intrahepatic Cholangiocarcinoma (Peking University, Cancer Cell 2019)](https://www.cbioportal.org/study/summary?id=hccihch_pku_2019) | Mix_23 | Mix_23T | A268S | Missense |

- **Other studies:** The other 10 studies have no non-R132 IDH1 mutations.
- **Overlapping cohorts:** Some of these studies overlap, for example the two TCGA cholangiocarcinoma studies and the two MSK intrahepatic studies, so patient counts across studies could double-count. None of the three hits above come from an overlapping pair.
- **Combined tumors:** The Peking University study covers combined hepatocellular and intrahepatic cholangiocarcinoma, not pure cholangiocarcinoma. Ignore that row if you want pure cholangiocarcinoma only.
- **Annotation:** I didn't check whether these variants are oncogenic or drivers. IDH1 R132 is the recurrent hotspot, and I have no functional annotation for these three.
- **Excluded:** I excluded the R132 hotspot by amino-acid position, so R132C, R132H, R132G and similar are all left out.

[View IDH1 non-R132 mutations across all 13 cholangiocarcinoma studies](https://www.cbioportal.org/results/mutations?cancer_study_list=chol_icgc_2017%2Cihch_msk_2021%2Cihch_mskcc_2020%2Cchol_msk_2018%2Chccihch_pku_2019%2Cihch_smmu_2014%2Cchol_tcga_gdc%2Cchol_tcga%2Cchol_jhu_2013%2Cchol_tcga_pan_can_atlas_2018%2Cchol_nccs_2013%2Cihch_ismms_2015%2Cchol_nus_2012&gene_list=IDH1%3A+MUT+%21%3D+R132&case_set_id=all). It opens the Mutations tab with a lollipop plot and mutation table.

If you'd like a single study or cohort instead, tell me which one and I'll narrow it.