Q (sonnet): Show me cases where PALB2 or ATM have germline mutations

▶ read_guide
{
 "uri": "cbioportal://germline-guide"
}

◀ result
Germline Variant Guide
======================

Overview
--------
cBioPortal stores both somatic AND germline variant data. Many cBioPortal features work identically for both variant types. This guide explains how to query germline variants and what to be aware of.

How Germline Data is Stored
---------------------------

### mutation_status is free text — always compare case-insensitively
Each study loads its own spelling. Germline calls appear as `'Germline'`, `'GERMLINE'` and `'germline'`; somatic calls as `'Somatic'`, `'SOMATIC'` and `'somatic'`; unannotated mutations as `'NA'`, `'.'`, `'Unknown'`, `'UNKNOWN'`, `'__UNKNOWN__'` and others. Matching one spelling silently drops whole studies (`mutation_status = 'Germline'` misses `all_stjude_2013`, `aml_stjude_2024` and `pog570_bcgsc_2020`).

- **Germline:** `upper(mutation_status) = 'GERMLINE'`
- **Somatic:** `upper(mutation_status) = 'SOMATIC'` — but only when the user asks for somatic-only. Many studies label their somatic calls `'NA'` or `'UNKNOWN'`, so for ordinary mutation questions follow common-pitfalls #3 and exclude only `'UNCALLED'`.
- When unsure, list the values first: `SELECT mutation_status, count() FROM genomic_event_derived WHERE cancer_study_identifier = '{study_id}' AND variant_type = 'mutation' GROUP BY mutation_status`

### Where the column lives
- `genomic_event_derived.mutation_status` (preferred): mutations, and structural variants (from `sv_status`: `'SOMATIC'`, `'Somatic'`, `'GERMLINE'`)
- `mutation_derived.mutationStatus`: the same values for mutations

Identifying Studies with Germline Data
--------------------------------------
Not all studies include germline data. Always check before querying:

```sql
-- Find studies containing germline mutations
SELECT cancer_study_identifier, COUNT(*) as germline_count
FROM genomic_event_derived
WHERE variant_type = 'mutation'
  AND upper(mutation_status) = 'GERMLINE'
GROUP BY cancer_study_identifier
ORDER BY germline_count DESC
```

Common Query Patterns
---------------------

### Count germline vs somatic mutations per gene in a study
```sql
SELECT hugo_gene_symbol, upper(mutation_status) AS status, COUNT(*) as count
FROM genomic_event_derived
WHERE cancer_study_identifier = '{study_id}'
  AND variant_type = 'mutation'
  AND upper(mutation_status) IN ('GERMLINE', 'SOMATIC')
GROUP BY hugo_gene_symbol, status
ORDER BY count DESC
LIMIT 20
```

### Find patients with germline mutations in a specific gene
```sql
SELECT DISTINCT patient_unique_id, sample_unique_id, mutation_variant, mutation_type
FROM genomic_event_derived
WHERE hugo_gene_symbol = '{GENE}'
  AND upper(mutation_status) = 'GERMLINE'
  AND cancer_study_identifier = '{study_id}'
  AND variant_type = 'mutation'
```

### Germline mutation frequency
The numerator is samples with a germline mutation in the gene; the denominator is samples **profiled** for the gene — not samples that happen to have a mutation in it. Take the denominator from mutation-frequency-guide Step 2 (or … (2222 more chars)

▶ clickhouse_run_select_query
{
 "query": "
SELECT
  cancer_study_identifier,
  patient_unique_id,
  sample_unique_id,
  hugo_gene_symbol,
  mutation_variant,
  mutation_type,
  mutation_status
FROM genomic_event_derived
WHERE hugo_gene_symbol IN ('PALB2', 'ATM')
  AND variant_type = 'mutation'
  AND upper(mutation_status) = 'GERMLINE'
ORDER BY cancer_study_identifier, hugo_gene_symbol, patient_unique_id
",
 "max_rows": 500
}

◀ result
{"rows":[{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-A2-A0T7","sample_unique_id":"brca_tcga_pub_TCGA-A2-A0T7-01","hugo_gene_symbol":"ATM","mutation_variant":"R3047*","mutation_type":"Nonsense_Mutation","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-A8-A08L","sample_unique_id":"brca_tcga_pub_TCGA-A8-A08L-01","hugo_gene_symbol":"ATM","mutation_variant":"G2023R","mutation_type":"Missense_Mutation","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-AN-A041","sample_unique_id":"brca_tcga_pub_TCGA-AN-A041-01","hugo_gene_symbol":"ATM","mutation_variant":"D1815Tfs*13","mutation_type":"Frame_Shift_Del","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-AN-A049","sample_unique_id":"brca_tcga_pub_TCGA-AN-A049-01","hugo_gene_symbol":"ATM","mutation_variant":"Q95*","mutation_type":"Nonsense_Mutation","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-AN-A0XL","sample_unique_id":"brca_tcga_pub_TCGA-AN-A0XL-01","hugo_gene_symbol":"ATM","mutation_variant":"X166_splice","mutation_type":"Splice_Site","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-B6-A0RV","sample_unique_id":"brca_tcga_pub_TCGA-B6-A0RV-01","hugo_gene_symbol":"ATM","mutation_variant":"X2032_splice","mutation_type":"Splice_Site","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-B6-A0WY","sample_unique_id":"brca_tcga_pub_TCGA-B6-A0WY-01","hugo_gene_symbol":"ATM","mutation_variant":"R2547_S2549del","mutation_type":"In_Frame_Del","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-BH-A0DD","sample_unique_id":"brca_tcga_pub_TCGA-BH-A0DD-01","hugo_gene_symbol":"ATM","mutation_variant":"R2912G","mutation_type":"Missense_Mutation","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-C8-A12X","sample_unique_id":"brca_tcga_pub_TCGA-C8-A12X-01","hugo_gene_symbol":"ATM","mutation_variant":"N1650S","mutation_type":"Missense_Mutation","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-D8-A13Z","sample_unique_id":"brca_tcga_pub_TCGA-D8-A13Z-01","hugo_gene_symbol":"ATM","mutation_variant":"X2544_splice","mutation_type":"Splice_Site","mutation_status":"Germline"},{"cancer_study_identifier":"brca_tcga_pub","patient_unique_id":"brca_tcga_pub_TCGA-E2-A154","sample_unique_id":"brca_tcga_pub_TCGA-E2-A154-01","hugo_gene_symbol":"ATM","mutation_variant":"G2023R","mutation_type":"Missense_Mutation","mutation_status":"Germline"},{"cancer_study_identifier":"kirc_tcga_pub","patient_unique_id":"kirc_tcga_pub_TCGA-B0-5097","sample_unique … (5376 more chars)

▶ clickhouse_run_select_query
{
 "query": "
SELECT cancer_study_identifier, hugo_gene_symbol, count(DISTINCT patient_unique_id) AS n_patients
FROM genomic_event_derived
WHERE hugo_gene_symbol IN ('PALB2', 'ATM')
  AND variant_type = 'mutation'
  AND upper(mutation_status) = 'GERMLINE'
GROUP BY cancer_study_identifier, hugo_gene_symbol
ORDER BY cancer_study_identifier, hugo_gene_symbol
"
}

◀ result
{"rows":[{"cancer_study_identifier":"brca_tcga_pub","hugo_gene_symbol":"ATM","n_patients":11},{"cancer_study_identifier":"kirc_tcga_pub","hugo_gene_symbol":"ATM","n_patients":3},{"cancer_study_identifier":"lung_nci_2022","hugo_gene_symbol":"ATM","n_patients":2},{"cancer_study_identifier":"pog570_bcgsc_2020","hugo_gene_symbol":"ATM","n_patients":6},{"cancer_study_identifier":"pog570_bcgsc_2020","hugo_gene_symbol":"PALB2","n_patients":2},{"cancer_study_identifier":"prad_su2c_2019","hugo_gene_symbol":"ATM","n_patients":7}]}

▶ resolve_and_route
{
 "studyIds": [
  "brca_tcga_pub",
  "kirc_tcga_pub",
  "lung_nci_2022",
  "pog570_bcgsc_2020",
  "prad_su2c_2019"
 ]
}

◀ result
{"success":true,"message":"Found 5 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":5,"studiesWithMetadata":[{"studyId":"brca_tcga_pub","name":"Breast Invasive Carcinoma (TCGA, Nature 2012)","sampleCount":825,"studyViewUrl":"https://www.cbioportal.org/study?id=brca_tcga_pub","metadata":{"clinicalAttributeIds":["AGE","CANCER_TYPE","CANCER_TYPE_DETAILED","CN_CLUSTER","CONVERTED_STAGE","ER_STATUS","FRACTION_GENOME_ALTERED","HER2_STATUS","INTEGRATED_CLUSTERS_NO_EXP","INTEGRATED_CLUSTERS_UNSUP_EXP","INTEGRATED_CLUSTERS_WITH_PAM50","METASTASIS","METASTASIS_CODED","METHYLATION_CLUSTER","MIRNA_CLUSTER","MUTATION_COUNT","NODES","NODE_CODED","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PAM50_SUBTYPE","PR_STATUS","RPPA_CLUSTER","SAMPLE_COUNT","SAMPLE_TYPE","SEX","SIGCLUST_INTRINSIC_MRNA","SIGCLUST_UNSUPERVISED_MRNA","SOMATIC_STATUS","SURVIVAL_DATA_FORM","TMB_NONSYNONYMOUS","TUMOR_STAGE","TUMOR_T1_CODED"],"molecularProfileIds":["brca_tcga_pub_gistic","brca_tcga_pub_linear_CNA","brca_tcga_pub_methylation_hm27","brca_tcga_pub_mirna","brca_tcga_pub_mirna_median_Zscores","brca_tcga_pub_mrna","brca_tcga_pub_mrna_median_Zscores","brca_tcga_pub_mrna_median_all_sample_Zscores","brca_tcga_pub_mrna_merged_median_Zscores","brca_tcga_pub_mutations","brca_tcga_pub_rppa","brca_tcga_pub_rppa_Zscores"],"heatmapProfileIds":["brca_tcga_pub_methylation_hm27","brca_tcga_pub_mrna_median_Zscores","brca_tcga_pub_mrna_median_all_sample_Zscores","brca_tcga_pub_mrna_merged_median_Zscores","brca_tcga_pub_rppa_Zscores"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations","mrna","protein","dna_methylation"]}},{"studyId":"kirc_tcga_pub","name":"Kidney Renal Clear Cell Carcinoma (TCGA, Nature 2013)","sampleCount":446,"studyViewUrl":"https://www.cbioportal.org/study?id=kirc_tcga_pub","metadata":{"clinicalAttributeIds":["CANCER_TYPE","CANCER_TYPE_DETAILED","FRACTION_GENOME_ALTERED","MUTATION_COUNT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","SAMPLE_COUNT","SAMPLE_TYPE","SOMATIC_STATUS","TMB_NONSYNONYMOUS"],"molecularProfileIds":["kirc_tcga_pub_gistic","kirc_tcga_pub_linear_CNA","kirc_tcga_pub_methylation_hm27","kirc_tcga_pub_mirna","kirc_tcga_pub_mirna_median_Zscores","kirc_tcga_pub_mrna","kirc_tcga_pub_mrna_median_Zscores","kirc_tcga_pub_mrna_median_all_sample_Zscores","kirc_tcga_pub_mrna_merged_median_Zscores","kirc_tcga_pub_mutations","kirc_tcga_pub_rna_seq_v2_mrna","kirc_tcga_pub_rna_seq_v2_mrna_median_Zscores","kirc_tcga_pub_rna_seq_v2_mrna_median_all_sample_Zscores","kirc_tcga_pub_rppa","kirc_tcga_pub_rppa_Zscores","kirc_tcga_pub_structural_variants"],"heatmapProfileIds":["kirc_tcga_pub_methylation_hm27","kirc_tcga_pub_mirna_median_Zscores","kirc_tcga_pub_mrna_median_Zscores","kirc_tcga_pub_mrna_median_all_sample_Zscores","kirc_tcga_pub_mrna_merged_median_Zscores","kirc_tcga_pub_rn … (3930 more chars)

▶ navigate_to_results_view
{
 "studyIds": [
  "brca_tcga_pub",
  "kirc_tcga_pub",
  "lung_nci_2022",
  "pog570_bcgsc_2020",
  "prad_su2c_2019"
 ],
 "genes": [
  "PALB2: MUT",
  "ATM: MUT"
 ],
 "tab": "mutations"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/results/mutations?cancer_study_list=brca_tcga_pub%2Ckirc_tcga_pub%2Clung_nci_2022%2Cpog570_bcgsc_2020%2Cprad_su2c_2019&gene_list=PALB2%3A+MUT%0AATM%3A+MUT&case_set_id=all","url":"https://www.cbioportal.org/results/mutations?cancer_study_list=brca_tcga_pub%2Ckirc_tcga_pub%2Clung_nci_2022%2Cpog570_bcgsc_2020%2Cprad_su2c_2019&gene_list=PALB2%3A+MUT%0AATM%3A+MUT&case_set_id=all","data":{"studyIds":["brca_tcga_pub","kirc_tcga_pub","lung_nci_2022","pog570_bcgsc_2020","prad_su2c_2019"],"studies":[{"studyId":"brca_tcga_pub","name":"Breast Invasive Carcinoma (TCGA, Nature 2012)","sampleCount":825},{"studyId":"kirc_tcga_pub","name":"Kidney Renal Clear Cell Carcinoma (TCGA, Nature 2013)","sampleCount":446},{"studyId":"lung_nci_2022","name":"Lung Cancer in Never Smokers (NCI, Nature Genetics 2021)","sampleCount":232},{"studyId":"pog570_bcgsc_2020","name":"Pan-cancer Analysis of Advanced and Metastatic Tumors (BCGSC, Nature Cancer 2020)","sampleCount":570},{"studyId":"prad_su2c_2019","name":"Metastatic Prostate Adenocarcinoma (SU2C/PCF Dream Team, PNAS 2019)","sampleCount":444}],"genes":["PALB2","ATM"],"caseSetId":"all","pageDescription":"Detailed mutation table with lollipop plot showing mutation positions, types, and frequencies for queried genes."}}

▶ navigate_to_study_view
{
 "studyIds": [
  "brca_tcga_pub",
  "kirc_tcga_pub",
  "lung_nci_2022",
  "pog570_bcgsc_2020",
  "prad_su2c_2019"
 ]
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/study/summary?id=brca_tcga_pub%2Ckirc_tcga_pub%2Clung_nci_2022%2Cpog570_bcgsc_2020%2Cprad_su2c_2019","url":"https://www.cbioportal.org/study/summary?id=brca_tcga_pub%2Ckirc_tcga_pub%2Clung_nci_2022%2Cpog570_bcgsc_2020%2Cprad_su2c_2019","data":{"studyIds":["brca_tcga_pub","kirc_tcga_pub","lung_nci_2022","pog570_bcgsc_2020","prad_su2c_2019"],"studies":[{"studyId":"brca_tcga_pub","name":"Breast Invasive Carcinoma (TCGA, Nature 2012)","sampleCount":825},{"studyId":"kirc_tcga_pub","name":"Kidney Renal Clear Cell Carcinoma (TCGA, Nature 2013)","sampleCount":446},{"studyId":"lung_nci_2022","name":"Lung Cancer in Never Smokers (NCI, Nature Genetics 2021)","sampleCount":232},{"studyId":"pog570_bcgsc_2020","name":"Pan-cancer Analysis of Advanced and Metastatic Tumors (BCGSC, Nature Cancer 2020)","sampleCount":570},{"studyId":"prad_su2c_2019","name":"Metastatic Prostate Adenocarcinoma (SU2C/PCF Dream Team, PNAS 2019)","sampleCount":444}],"tab":"summary","hasFilters":false,"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."}}

═ answer (success)
Note: the ResultsView link above queries all PALB2/ATM mutations (somatic + germline combined), since cBioPortal's OQL doesn't filter by germline status directly — use it to browse the mutation table, but the germline-specific counts below are from the underlying data.

## Germline PALB2/ATM Mutations Across cBioPortal

I found **31 patients** with germline mutations in ATM or PALB2, spanning **5 studies** (no single study or cancer type was specified, so this covers the full database):

| Study | Gene | Patients (germline) |
|---|---|---|
| [Breast Invasive Carcinoma (TCGA, Nature 2012)](https://www.cbioportal.org/study/summary?id=brca_tcga_pub) | ATM | 11 |
| [Kidney Renal Clear Cell Carcinoma (TCGA, Nature 2013)](https://www.cbioportal.org/study/summary?id=kirc_tcga_pub) | ATM | 3 |
| [Lung Cancer in Never Smokers (NCI, 2021)](https://www.cbioportal.org/study/summary?id=lung_nci_2022) | ATM | 2 |
| [Pan-cancer Analysis of Advanced/Metastatic Tumors (POG570, BCGSC 2020)](https://www.cbioportal.org/study/summary?id=pog570_bcgsc_2020) | ATM | 6 |
| [Pan-cancer Analysis of Advanced/Metastatic Tumors (POG570, BCGSC 2020)](https://www.cbioportal.org/study/summary?id=pog570_bcgsc_2020) | PALB2 | 2 |
| [Metastatic Prostate Adenocarcinoma (SU2C/PCF, PNAS 2019)](https://www.cbioportal.org/study/summary?id=prad_su2c_2019) | ATM | 7 |

**Notable individual variants:**
- **ATM**: recurrent truncating events (nonsense, frameshift, splice-site) at multiple codons — e.g., R3047\*, Q95\*, several splice-site losses (X974_splice, X2544_splice) — plus missense variants like G2023R (seen twice, in `brca_tcga_pub`) and E2052K.
- **PALB2**: only 2 germline cases, both in the POG570 cohort — a frameshift deletion (D595Mfs\*4) and a splice-site variant.

No germline PALB2 or ATM mutations were found in any other study currently loaded in cBioPortal — this reflects that most studies either don't distinguish germline from somatic calls, or don't include germline variant data at all (germline sequencing/reporting is study-specific).

**Links:**
- [Mutations tab — PALB2/ATM across all 5 studies](https://www.cbioportal.org/results/mutations?cancer_study_list=brca_tcga_pub%2Ckirc_tcga_pub%2Clung_nci_2022%2Cpog570_bcgsc_2020%2Cprad_su2c_2019&gene_list=PALB2%3A+MUT%0AATM%3A+MUT&case_set_id=all) — lollipop plot and mutation table (note: this view shows all mutations, not filtered to germline only; use the table above to identify the germline cases)
- [Study View — all 5 cohorts](https://www.cbioportal.org/study/summary?id=brca_tcga_pub%2Ckirc_tcga_pub%2Clung_nci_2022%2Cpog570_bcgsc_2020%2Cprad_su2c_2019) — cohort overview and clinical data

*Caveat:* combined sample totals across these 5 studies are not additive for prevalence purposes since cohorts don't overlap here, but germline annotation practices differ by study, so absence of germline calls elsewhere doesn't mean absence of the mutations themselves — only that germline/somatic origin wasn't distinguished in those datasets.