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Golden examples (CI-diffed)

Three end-to-end runs of the variant clinical-report pipeline (generate_variant_clinical_report) against canonical variants, pinned as regression fixtures and diffed in CI. Unlike the illustrative transcripts, these are executed and asserted on every run.

# Variant Interpretive class Pipeline tier ClinVar
01 BRCA1 c.5266dupC (p.Gln1756fs) germline loss-of-function founder allele HIGH Pathogenic (expert panel)
02 TP53 p.Arg175His (c.524G>A) somatic structural hotspot HIGH Pathogenic (expert panel)
03 EGFR p.Leu858Arg (c.2573T>G) somatic activating driver MEDIUM Not provided (germline)

Full write-ups — canonical identifiers, established classification with cited primary literature, and a point-by-point concordance analysis of pipeline output vs. ground truth — live with each example under examples/golden/.

How they work

scripts/record_golden_examples.py runs each variant through the live public APIs once and records the traffic at the client's _request boundary (past the retry loop, so one clean request/response per call), each response tagged with a SHA-256 of its body. The golden test (tests/golden/test_golden_examples.py) replays those recorded responses through respx, entirely offline, and asserts the pipeline reproduces the committed expected.json. The only redacted fields are the provenance version and timestamp; every scientific field must match exactly or CI fails. The test is deterministic across Python hash seeds.

What they establish — and what they do not

They pin pipeline behaviour on canonical inputs and give worked, source-traceable examples; a future drift in any scientific field is caught in CI. They are a regression and traceability artifact, not independent scientific validation of the druggability or ACMG heuristics — that remains roadmap items 3–4 (external review; benchmark calibration). Each example keeps a strict line between what the pipeline computes (over public data) and the established literature, and flags any divergence.

The three span the interpretive space deliberately. Example 03 (EGFR L858R) is the sharpest: ClinVar carries no germline pathogenicity assertion for it (its significance is somatic/therapeutic — Tier I, TKI-sensitizing), so the pipeline correctly declines a germline-pathogenic call and lands at MEDIUM on computational evidence alone. Example 01 (BRCA1) is also what surfaced and motivated the ClinVar exact-record resolution fix.