TESTING HUB

From swab to sequencer: choosing a hereditary-cancer test

A calm, citation-minded walk through the kit landscape — clinical sequencing, direct-to-consumer screens, multi-gene panels, and how to read what comes back. The PROMPT Registry desk explains the evidence; your clinician and genetic counsellor make the call.

Compare clinical vs. DTC How panels work

~72%

cumulative breast-cancer risk to age 80 in <code>BRCA1</code> carriers

Kuchenbaecker et al., cited in JCO/PROMPT literature

~53%

lifetime breast-cancer risk with pathogenic <code>PALB2</code> variants

NCBI / GeneReviews

>90%

of pathogenic variants missed by a 3-variant <code>BRCA</code> DTC screen vs. full sequencing

JCO Precision Oncology 2022

~110 µg

median DNA yield from a 2 mL <code>OG-500</code> saliva sample

DNA Genotek

swab → sequencer

WHY THIS HUB EXISTS

A test is only as good as its scope — and its interpretation

The same patient, the same swab, can yield very different answers depending on which kit is used and how the laboratory classifies what it finds. A direct-to-consumer screen authorised only for three Ashkenazi-Jewish founder variants in BRCA1 and BRCA2 is not the same instrument as a CLIA-certified multi-gene panel sequencing twenty-plus genes end to end.

The PROMPT Registry — the Prospective Registry Of MultiPlex Testing, a multi-institution hereditary-cancer registry whose findings appear in ASCO/JCO — was built precisely to follow people carrying variants in lesser-known panel genes such as ATM, CHEK2, PALB2 and RAD51C. This page distils that lineage into a kit-by-kit comparison. It is an educational explainer, not medical advice.

Read our approach

Four routes through the testing landscape

Each spoke below takes one decision and works it through with real figures. Start wherever your question sits.

ACCESS & ACCURACY01

Clinical vs. direct-to-consumer

Why a CLIA/CAP clinical test and a consumer screen answer different questions — scope of variants, false-negative risk, and why confirmatory testing is advised.

Compare the two

PANEL DESIGN02

Multi-gene panel kits

What a 20-gene hereditary-cancer panel actually sequences, from BRCA1 to TP53, and how diagnostic yield trades against variants of uncertain significance.

Inside the panel

FOUNDATIONS03

BRCA testing explained

The two genes that anchor hereditary breast-and-ovarian cancer — what pathogenic variants in BRCA1/BRCA2 mean for lifetime risk, and what they do not.

Start with BRCA

INTERPRETATION04

Reading your results

The five-tier ACMG ladder from Pathogenic to Benign, why a VUS is not a diagnosis, and how to take a report to a genetic counsellor.

Decode a report

Sample-collection methods at a glance

The first decision in any kit is what tissue it samples and how that sample survives transit. Figures reflect manufacturer technical specifications and peer-reviewed stability data.

Method	Typical sample	DNA yield (indicative)	Room-temp stability	Notes
Saliva (`OG-500`)	2 mL	~110 µg median	Years at room temperature	All-in-one collect/stabilise/transport; postable. Yield varies by donor.
Buccal swab	Cheek epithelium	Lower, more variable	~360 days demonstrated in buffer	Less invasive; lower cellularity than saliva.
Blood draw (EDTA vacutainer)	3–10 mL whole blood	Highest, most consistent	Hours–days; refrigerate	Clinical gold standard for yield and quality; needs phlebotomy.

Table 1. Common hereditary-cancer sample types and their handling characteristics.

Lifetime breast-cancer risk by gene (indicative ranges)

Penetrance differs sharply across the genes a panel covers — one reason panels report each finding gene-by-gene rather than as a single score. Values are approximate lifetime/cumulative estimates from the published literature and vary by study and population.

BRCA172 %

cumulative to age 80 (Kuchenbaecker et al.)

PALB253 %

lifetime, pathogenic carriers

CHEK237 %

lifetime, pathogenic carriers

General population (reference)13 %

~1 in 8, lifetime (NCI)

The ACMG five-tier ladder

Every variant a laboratory sequences is classified against the 2015 ACMG/AMP framework. Knowing the rung matters more than knowing the gene.

Pathogenic (P): Known to cause disease; meets the strongest combinations of ACMG criteria (e.g. PVS1 with supporting evidence).
Likely pathogenic (LP): >90% probability of being disease-causing; managed clinically much like Pathogenic.
VUS: Variant of uncertain significance — evidence is conflicting or insufficient. Not a diagnosis and not actionable on its own; this is the category PROMPT was built to resolve over time.
Likely benign (LB): >90% probability of being harmless.
Benign (B): Known to be harmless; the stand-alone criterion BA1 can settle this outright.

Pick the kit that answers your question

The four spokes above each end with a counsellor signpost. None of this replaces a personal conversation with a clinician or certified genetic counsellor — it helps you arrive at one better informed.

Browse all guides

References

[1]JCO Precision Oncology 2022. Retrospective cohort on the limitations of direct-to-consumer genetic screening in hereditary breast and ovarian cancer — three-variant screens miss >90% of pathogenic variants versus full sequencing.↗
[2]ACMG/AMP 2015. Richards S et al. Standards and Guidelines for the Interpretation of Sequence Variants — the five-tier P/LP/VUS/LB/B framework.↗
[3]ASCO / JCO (PROMPT). Domchek SM, Robson ME et al. Prospective Registry Of MultiPlex Testing (PROMPT): a web-based platform to assess cancer risk of genetic variants.↗
[4]GeneReviews / NCBI. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer; PALB2 and CHEK2 penetrance estimates.↗
[5]DNA Genotek. Oragene OG-500 technical specifications — saliva DNA yield and room-temperature stability.↗