Genetic diagnostics, from swab to sequencer
An evidence desk on hereditary-cancer testing, in the heritage of the Prospective Registry of Multiplex Testing — a real multi-institution registry whose findings on multi-gene panels are cited across ASCO and the Journal of Clinical Oncology. Explainers only; for personal decisions, see a clinician or genetic counsellor.
The four diagnostics hubs
We follow a single specimen along its path — how it is collected, what is tested, how the lab reads it, and how it travels safely. Each hub gathers the evidence for one leg of that journey.
Collection
Saliva kits, buccal swabs, and blood draws — yield, stabilising buffers, and what a usable specimen actually requires.
Enter the hubTesting
Clinical vs direct-to-consumer testing, multi-gene panels, BRCA1/BRCA2 explained, and reading a result without over-reading it.
Lab
From DNA extraction to sequencing flow cells — plates, reagents, pipettes, and the depth at which variants are called.
Logistics
Biohazard shipping containers, preservation buffers, and cold-chain handling that keep a sample analysable in transit.
Enter the hubFrom swab to sequencer
A simplified view of the path a hereditary-cancer specimen takes through the diagnostic chain.
- 01
Collect
A saliva kit such as
OG-500captures ~2 mL of sample, mixed on the spot with a stabilising buffer so cells lyse cleanly and nucleases are held in check. - 02
Stabilise & ship
Stabilised saliva is room-temperature stable for months, letting samples travel by post in
UN3373biological-substance packaging rather than on ice. - 03
Extract
In the lab,
DNAis purified from the lysate; saliva typically yields more totalDNAthan a buccal swab, easing downstream library prep. - 04
Sequence
A targeted panel is sequenced — commonly to ~500× mean depth — so heterozygous germline variants are called with confidence across genes like
BRCA1,BRCA2,PALB2,CHEK2, andATM. - 05
Classify & report
Each variant is graded against ACMG/AMP criteria into one of five tiers, from benign to pathogenic — with uncertain calls flagged rather than forced.
Collection methods compared
Yield and stability differ by method; figures below reflect manufacturer technical specifications and peer-reviewed comparisons, and vary by donor and handling.
| Method | Sample | Typical DNA yield | Stability | Notes |
|---|---|---|---|---|
Stabilised saliva (OG-500) | ~2 mL | ~110 µg (range ~15–300+ µg) | Room temp, up to ~30 months | Non-invasive; highest typical total yield |
| Buccal swab | Cheek scrape | Lower than saliva | Days–weeks (kit-dependent) | Convenient but lower yield |
Blood draw (EDTA) | ~2–10 mL | High, high-purity | Refrigerated; days unfrozen | Gold-standard purity; venipuncture required |
Table 1. Indicative DNA yield and stability by collection method.
Lifetime breast-cancer risk: carriers vs general population
Approximate lifetime female breast-cancer risk. General-population and BRCA carrier figures per NCI; carrier risk commonly cited as exceeding 60%.
How a result is graded
The 2015 ACMG/AMP framework sorts germline sequence variants into five tiers — the language behind every line of a panel report.
- Pathogenic (P)
- Strong, combined evidence that the variant causes disease.
- Likely pathogenic (LP)
- High probability (commonly ~90%+) of being disease-causing, short of certainty.
- VUS
- Variant of uncertain significance — insufficient evidence to call either way; not a basis for action on its own. The PROMPT registry was built in part to track these over time.
- Likely benign (LB)
- Evidence leans against a clinical effect.
- Benign (B)
- Considered not to cause the condition.
About the PROMPT Registry
The Prospective Registry of Multiplex Testing (PROMPT) is a real, multi-institution registry launched in 2014 for people who underwent multi-gene panel testing for cancer susceptibility. Participants carrying pathogenic variants or a VUS self-enrolled, and the registry followed them over time — work cited across ASCO meetings and the Journal of Clinical Oncology.
This desk honours that lineage as an educational explainer. We do not run the original study, we are not enrolling participants, and nothing here is medical advice. For your own testing or results, speak with a clinician or genetic counsellor.
Latest from the registry
Recent explainers from the research desk — plain-language reads on the evidence behind hereditary-cancer diagnostics.
BRCA testing, explained
What a BRCA1/BRCA2 result does and doesn't tell you, and why penetrance is a range, not a verdict.
Reading your results
Pathogenic, likely pathogenic, VUS — how the five ACMG tiers translate to next steps with a counsellor.
Sample stability & storage
Why a stabilising buffer matters, and how long a stabilised saliva sample really lasts at room temperature.
Read“A variant of uncertain significance is not a diagnosis — it is a question the evidence has not yet answered. Registries exist to keep asking it.”
Start at the diagnostics hub
Trace a specimen from swab to sequencer, hub by hub — collection, testing, lab, logistics. Evidence-led, citation-minded, and free of sales.