From swab to sequencer
A plain-spoken map of hereditary-cancer testing: how a saliva tube or buccal swab becomes sequenced data, how laboratories classify what they find, and how a report finally reaches a clinic. Educational explainers, citation-minded, never a sales pitch.
The end-to-end workflow
Every hereditary-cancer result travels the same path. Understanding each handoff makes a report far less opaque — and explains why turnaround takes weeks, not minutes.
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1 · Indication & counselling
A personal or family history flags possible hereditary risk. A clinician or genetic counsellor frames what a test can and cannot answer before any sample is taken.
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2 · Collection
DNA is captured from saliva (
OG-500), a buccal swab, or a blood draw (EDTAvacutainer). The choice trades sample yield against convenience and stability. - 03
3 · Stabilise & ship
Lysis or preservation buffer protects the DNA; the tube is triple-packed as
UN3373Category B and shipped at ambient temperature under packing instructionP650. - 04
4 · Extraction
The lab isolates genomic DNA, checks yield and purity (A260/A280), and normalises concentration before library preparation.
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5 · Sequencing
A targeted multi-gene panel is enriched and read on a flow cell — typically ~100× depth for germline panels, against the ~30× standard for whole-genome sequencing.
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6 · Variant calling & classification
Reads are aligned, variants called, then each is graded against the ACMG/AMP framework: Pathogenic, Likely pathogenic,
VUS, Likely benign, or Benign. - 07
7 · Report & return
A clinical report goes back to the ordering clinician, who interprets findings in context — risk figures, surveillance options, and onward referral.
The four hubs
Our explainers cluster into four areas of the journey. Each hub links to focused spoke topics you can read in any order.
Getting DNA out of the body
Saliva kits, buccal swabs, blood-draw vacutainers, and how sample type drives yield, comfort, and shelf life.
Collection hubWhat the test actually asks
Clinical vs direct-to-consumer testing, multi-gene panels, BRCA explained, and how to read your results without panic.
Testing hubInside the laboratory
Extraction kits, PCR plates and reagents, pipettes and tips, and the sequencing flow cells that read the library.
Lab hubMoving samples safely
Biohazard shipping containers, preservation buffers, cold-chain handling, and the regulations behind UN3373 transport.
Collection methods at a glance
The first decision in any workflow is how to capture DNA. Yields and stability below reflect manufacturer technical specifications and common laboratory practice; treat them as typical ranges, not guarantees.
| Method | Typical sample | Stability | Notes |
|---|---|---|---|
Saliva — OG-500 | ~2 mL saliva + buffer | Years at room temperature | High total yield; lysis buffer stabilises DNA immediately on capping. |
| Buccal swab | Cheek-cell scrape | Weeks, ambient (dry/buffered) | Low burden, child-friendly; lower yield than saliva. |
Blood draw — EDTA vacutainer | 2–10 mL whole blood | Days refrigerated; longer if processed | Highest-quality DNA; needs phlebotomy and tighter handling. |
Table 1. Common germline DNA collection methods and their handling profile.
Sequencing depth by approach
"Depth" is how many times each base is read. Higher depth means more confident variant calls — targeted hereditary-cancer panels are read far deeper than a whole genome to maximise sensitivity over a focused set of genes.
≥30× gold standard for SNV/indel discovery
≥50× recommended, ~100× preferred
Deep coverage over a curated gene set
What "Pathogenic" — and "uncertain" — really mean
A sequenced variant is not a verdict on its own. Under the 2015 ACMG/AMP framework, laboratories weigh up to 28 criteria — population frequency, computational prediction, functional and segregation data — to place each variant in one of five tiers: Pathogenic, Likely pathogenic, Variant of Uncertain Significance (VUS), Likely benign, or Benign. The "likely" tiers carry a target confidence of about 90%.
A VUS is the honest middle: real, but not yet understood. It is not a diagnosis, and classifications can be revised as evidence accumulates — one reason the original PROMPT registry mattered. Personal decisions belong with a clinician or genetic counsellor, not a label alone.
“A registry's value is the boring part: tracking the same variant across many people and many years, so a result classed "uncertain" today can be resolved tomorrow.”
Begin at the beginning
Follow the pathway in order, or jump to the hub that answers your question. Everything here is an educational explainer — for a personal decision, speak with a clinician or genetic counsellor.