clinvar

ClinVar Evidence

Use this skill when the user asks about clinical labels, carrier findings, pathogenic/likely pathogenic entries, VUS, conflicting classifications, drug response, risk-factor labels, or ClinVar-derived discovery.

Goal

Build a candidate landscape from exact ClinVar matches. Use candidate_inventory as variant-level provenance evidence and candidate_review_groups as the carrier/condition review inventory.

Convention: See skills/conventions/evidence-quality.md.

Contract

• ClinVar matches provide exact/static evidence for source-backed interpretation.
• Exact matching requires the optional build-specific library clinvar-grch38 or clinvar-grch37.
• Candidate inventories are variant-level evidence, not interpretation.
• Candidate review groups are review targets. A heterozygous P/LP group can be carrier-relevance evidence; it is not a carrier-status conclusion.
• clinvar.scan_candidates returns an evidence view, grouped support, warnings, and coverage; use those fields rather than inferring priority from prose.
• By default, clinvar.scan_candidates includes P/LP, conflicting, VUS, risk/association/protective, drug-response, and benign ClinVar groups.
• If ClinVar matches are missing, clinvar.scan_candidates materializes them from the Active Genome Index before building the candidate inventory.
• VUS, conflicts, and low-review assertions are downgraded unless reviewed source evidence supports a stronger claim.
• Drug-response rows use pharmacogenomic source context before actionability is implied.

Cross-Capability Synthesis

A scope-limited result from this capability is not a final user-facing answer when other Genomi capabilities can contribute orthogonal evidence to the same question. Returning "cannot answer" while applicable capabilities remain unexamined is a host-agent failure mode.

Tools

clinvar.match_variants

Materialize exact ClinVar matches for comparable Active Genome Index variants using the installed build-specific ClinVar library.

Use when: After an Active Genome Index and the matching build-specific ClinVar library are available to materialize exact ClinVar/sample matches.

Why necessary: ClinVar matching is library-scoped materialization; it turns installed public ClinVar rows into exact matches for an Active Genome Index without forcing every genome-artifact task to run ClinVar.

clinvar.scan_candidates

Build a deterministic candidate inventory and candidate review groups from exact ClinVar matches, materializing those matches from the Active Genome Index when needed.

Use when: Broad Active Genome Index disease or risk triage when exact ClinVar candidate inventory is needed.

Why necessary: Broad disease triage needs bounded ClinVar variant provenance plus review groups instead of ad hoc spot checks over a large genome file. It performs missing match materialization internally before candidate scanning.

Interpretation Rules

• Pathogenic/likely pathogenic labels need zygosity, inheritance, population frequency, gene-disease context, and source quality.
• Carrier language belongs in phenotype.plan_risk_investigation with investigation_type:"carrier_review" after reviewing the group gates.
• VUS and conflicting labels use uncertainty/conflict wording.
• Drug-response labels require pharmacogenomic guideline context before clinical actionability is implied.
• Common association/risk/protective labels usually provide limited context for personal common-disease risk.

Routing Checks

• Prioritize ClinVar matches by actionability, review status, uncertainty, population context, inheritance, and zygosity.
• If a ClinVar operation returns status="requires_library_install", explain how the named library helps this request and ask before installing it.
• Treat ClinVar condition strings as database labels that need interpretation.
• Keep the whole candidate inventory local; send selected public targets to Journal source-review memory.