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+ Click a variant to open its details page; the boxed link goes straight to the CIViC page for that item.
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+ The CIViC page for BRAF V600E: click a variant for more, and read the diseases and therapies associated with each.
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+ Click an Evidence ID (EID) in the list to open its full evidence record.
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+ Click a variant in the ClinVar interp track for its details page, then follow the link out to the variant's full record on ClinVar.
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+ Lollipop track of somatic mutations; click a lollipop for its mouse-over and the item details (here C>T, seen in 38 samples).
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+ The GenCC track: gene-disease links coloured by evidence strength.
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+ Click a feature for its details, then follow the boxed link straight to the GenCC page for the gene.
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+UCSC Genome Browser · Tutorial 2
+Cancer Data
+The cancer & clinical databases, worked on BRAF V600E
+A hands-on tour of the oncology tracks · genome.ucsc.edu
+What we'll cover
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- How to analyse variants using the cancer database tracks. +
- The main tracks: CIViC, COSMIC, ClinVar, TCGA (somatic) and GenCC, OMIM, gnomAD (germline). +
- A running example throughout: BRAF V600E, the well-known melanoma driver. +
- Where each database fits when you ask “is this variant real, and does it matter?” +
Two kinds of question
+ We split the databases into somatic (acquired, in cancer) and germline (inherited) diagnosis.
+Where the cancer data lives
+The key datasets and what each is good for. Click a name for its track description page.
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+ Clinical & cancer databases
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- ClinVar: archive of lab and expert-panel variant classifications. Is it already called pathogenic, benign, or VUS (and now its somatic oncogenicity)? +
- COSMIC: catalogue of somatic mutations in cancer. Shows how recurrently a site is mutated across tumours, flagging likely drivers. +
- CIViC: crowd-sourced, expert-curated clinical interpretations. Is the variant oncogenic and linked to a therapy? +
- GenCC: curated gene-disease validity with evidence strength. Is the gene genuinely tied to a heritable disease? +
- OMIM: genes and Mendelian phenotypes. The reference for known gene-disease relationships and disease alleles. +
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+ Population frequency & evidence
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- TCGA Pan-Cancer: somatic mutations across ~10,000 tumours of many types, drawn as a lollipop. Shows recurrence and hotspots by cancer type. +
- gnomAD: population allele frequencies from large healthy cohorts. Common implies benign, and it filters germline variants out of somatic calls. +
- UniProt: protein domains and key residues. Does the variant fall in a functional region (ACMG PM1)? +
- REVEL: ensemble missense pathogenicity score (0 to 1). High values support a damaging computational call (PP3). +
- Conservation (100-way): cross-species constraint. Conserved positions are more likely functionally important. +
Somatic diagnosis
+Somatic variants
+acquired mutations: SNVs, de novo changes, and cancer drivers
+CIViC: Clinical Interpretation of Variants in Cancer
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+ Hover a variant in the CIViC track to see its associated therapies and diseases.
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- Collaborative and expert-reviewed: submissions are vetted by editors and the community. +
- Links each variant to diseases, drugs and therapies. +
- Every claim carries a cited publication as evidence. +
- Best for: is this variant oncogenic and linked to a therapy? +
Try it, ▶ open the BRAF CIViC session
+ Hover a variant to preview its therapies and diseases.
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+ CIViC: click a feature for the details
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+ CIViC: the page for BRAF V600E
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+ CIViC: the evidence behind each call
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+ Each disease and therapy links to Evidence Items (EIDs); each EID cites the supporting publication and rates its strength: the “show me the evidence” layer behind actionability.
+ +COSMIC: Catalogue of Somatic Mutations in Cancer
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COSMIC in the Browser: recurrent somatic mutations across cancer types.
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- The reference catalogue of somatic mutations seen across tumours. +
- Shows how recurrently a position is mutated, and in which cancer types. +
- Best for: spotting recurrent hotspots and likely drivers. +
Try it, ▶ open COSMIC at the BRAF hotspot
+ The V600 hotspot stands out by recurrence.
+ ClinVar: variant-disease classifications
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The ClinVar track across a gene, coloured by clinical significance. 
At BRAF V600E: pathogenic submissions (T>A).
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- Public archive of submitted clinical classifications, pathogenic to benign, with review status. +
- Increasingly carries somatic oncogenicity and clinical-impact calls. +
- Click a variant for its interpretation and submitters. +
Try it, ▶ open the BRAF ClinVar interpretation track
+ Variants coloured by clinical significance.
+ ClinVar database link
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+ TCGA Pan-Cancer
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- Somatic variants across thousands of tumours and many cancer types; useful for variant frequency by cancer type. +
- Drawn as a lollipop plot; mouse-over identifies the variant and its sample count. +
COSMIC vs TCGA
+ Both show recurrence. TCGA is one uniform cohort with comparable, by-cancer-type frequencies; COSMIC is the broader aggregate catalogue (bigger counts plus the driver Census), but heterogeneous.
+ Try it, ▶ open TCGA Pan-Cancer at BRAF
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+ Germline diagnosis
+Germline variants
+inherited disease: gene-level validity and population frequency
+GenCC: the Gene Curation Coalition
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- Aggregates gene-disease validity from many expert groups. +
- Germline / Mendelian focus: genes to inherited diseases, not specific variants or somatic mutations. +
- Colour = strength of the link (definitive, strong, moderate, limited); spans the whole gene, mouse-over for the curated detail. +
Try it, ▶ open the GenCC BRAF session
+ The gene-disease links for BRAF, coloured by evidence.
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+ GenCC: click through to the source
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+ OMIM: Online Mendelian Inheritance in Man
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OMIM in the Browser: gene-phenotype relationships and known disease alleles.
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- The classic catalogue of human genes and their phenotypes. +
- Mostly inherited disease; well-known genes (e.g. BRAF) can list somatic phenotypes too. +
- Covers whole-gene phenotype links and specific alleles. +
OMIM vs GenCC
+ OMIM gives per-gene depth (narrative biology and specific disease alleles); GenCC gives the standardized gene-disease validity tier and is fed partly by OMIM.
+ Try it, ▶ open OMIM at BRAF
+ gnomAD: Genome Aggregation Database
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gnomAD variants across a gene. 
Mouse-over: allele frequency, filter status and ancestry.
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- Allele frequencies from large, broadly healthy populations (the “normal” database). +
- A variant common here is most likely benign. +
- In cancer, used to filter germline and common variants out of somatic calls. +
Where to next
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- These databases come together in Tutorial 3: Clinical Examples & Variant Interpretation, where we work full examples end to end. +
- Help → Interactive Tutorials, or the docs at genome.ucsc.edu/docs. +
- Email the team: genome@soe.ucsc.edu. +
Thank you!
+Questions? · genome@soe.ucsc.edu
+UCSC Genome Browser · genome.ucsc.edu
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