Documentation / Classification / ClinVar Integration
ClinVar Integration
Three Uses of ClinVar Data
As evidence criteria
PS1 (strong, 2+ stars), PP5 (supporting, 1 star), BP6 (supporting, 1+ star). ClinVar assertions contribute to the Bayesian point total alongside all other criteria.
As classification override
When no conflicting computational evidence exists, ClinVar assertions with sufficient review stars can determine the final classification directly.
As quality filter rescue
ClinVar Pathogenic/Likely Pathogenic variants are never discarded by quality filtering, regardless of sequencing quality metrics.
ClinVar Override Conditions
Override IS applied when:
ClinVar asserts P/LP/B/LB with at least 1 review star
No conflicting computational evidence exists
BA1 does not apply
Override is NOT applied when:
BA1 applies (frequency > 5% always overrides ClinVar)
Conflicting pathogenic + benign evidence exists
ClinVar asserts VUS
Review stars below minimum threshold
Review Stars Explained
| Stars | Meaning |
|---|---|
| 0 | Single submitter, no assertion criteria provided |
| 1 | Single submitter with assertion criteria, or multiple submitters with conflicting interpretations |
| 2 | Multiple submitters, no conflict, assertion criteria provided |
| 3 | Reviewed by expert panel |
| 4 | Practice guideline |
Evidence Transparency
When ClinVar classification is used, the criteria string includes "ClinVar" as the first element (e.g., "ClinVar,PM2,PP3") to make the evidence source explicit. The review star level is displayed alongside every variant for the reviewing geneticist to assess assertion quality independently.
Important Caveat
ClinVar assertions vary in quality and may lag behind current evidence. Review star levels indicate the level of review, not the correctness of the assertion. The geneticist should assess ClinVar assertion quality independently, particularly for 0-star and 1-star submissions. The current ClinVar version in production is 2025-01.