Evidence first, plain language always
How this resource sources, weighs, and translates hereditary-cancer testing science — from peer-reviewed registries to ACMG variant criteria — without a single product to sell.
“Two laboratories can read the same variant and reach different conclusions. Our job is to show readers where the evidence is settled, where it is still moving, and how to tell the difference.”
How a claim becomes a page
Every explainer on this site moves through the same editorial method — the same path a sample takes from swab to sequencer, applied to evidence instead of DNA.
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1 · Source from primary literature
We start with peer-reviewed work and guideline bodies — NCI, ACMG/AMP, NCCN, NHGRI, and ASCO/JCO publications such as the PROMPT registry itself. Press releases and vendor copy are never a primary source.
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2 · Weigh the evidence level
Risk figures are reported as ranges with their study context, not single hero numbers. We note sample size, population, and whether a finding is a consensus guideline or a single cohort.
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3 · Translate to plain language
Technical tokens — gene names like
PALB2, variant IDs likers80357906, kit codes likeOG-500— are kept exact but explained in plain words on first use. - 04
4 · Separate education from decision
We explain what tests measure and what terms mean. We never recommend a personal course of action — that belongs with a clinician or genetic counsellor who knows your history.
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5 · Cite, date, and revisit
Each page carries numbered references with links. Variant science changes; pages note when a figure reflects a point-in-time classification rather than a fixed fact.
What we report, and how we qualify it
A worked example of the editorial standard: the same hereditary-breast-cancer genes, with the qualifiers we attach so a range is never mistaken for a verdict.
| Gene | Risk tier | Reported lifetime range | How we qualify it |
|---|---|---|---|
BRCA1 / BRCA2 | High penetrance | ~60–80% | Cite as a range; flag dependence on family history and ascertainment |
PALB2 | High penetrance | Similar magnitude to BRCA2 | State the comparison, not a fixed percent, where sources do |
CHEK2 | Moderate penetrance | ~2–3× baseline | Express as relative risk; avoid implying a single absolute number |
ATM | Moderate penetrance | Elevated; estimates evolving | Mark as an area of active research; date the estimate |
Table 1. Illustrative lifetime breast-cancer risk by gene, with editorial qualifiers. Figures are population estimates that vary by study, family history, and ancestry — not individual predictions.
Why variant interpretation needs careful sourcing
From the PROMPT registry's own catalogue — the spread of classifications shows why we report uncertainty honestly rather than rounding it away. A large share of variants are simply not yet resolved.
Clinically actionable
Not yet resolved — the largest group
Labs disagree
Reassuring
Key terms, defined the way we use them
A few load-bearing terms. Full definitions live in the glossary; these are the ones the method depends on.
- VUS
- Variant of uncertain significance — a change in a gene such as
CHEK2whose effect on cancer risk is not yet established. We treat a VUS as a question, never as a diagnosis. - Penetrance
- The proportion of people carrying a variant who actually develop the associated condition. High-penetrance genes like
BRCA1differ sharply from moderate-penetrance genes likeATM. - ACMG/AMP tiers
- The five-tier framework (pathogenic, likely pathogenic, uncertain, likely benign, benign) published by the American College of Medical Genetics and the Association for Molecular Pathology in 2015, built from 28 weighted evidence criteria.
- Multiplex / panel testing
- Sequencing several genes at once — e.g.
ATM,CHEK2,PALB2,BRIP1— rather than one gene in isolation. The basis of the PROMPT registry's data. - Analytic vs. clinical validity
- Whether a test reliably detects what it claims (analytic) versus whether the result meaningfully predicts an outcome (clinical). We keep the two distinct.
Our stance, in plain terms
Do you sell tests, kits, or sequencing services?
No. This is an editorial resource in its authority phase — there are no product links, affiliate codes, or shop pages anywhere on the site. Kit codes such as OG-500 appear only as technical references, not recommendations to buy.
Is the original PROMPT study still enrolling?
We make no such claim. PROMPT (Prospective Registry of Multiplex Testing) is a real multi-institution hereditary-cancer registry whose findings were published through ASCO/JCO. We honour that heritage and cite its data; we do not represent it as currently recruiting.
How do you handle conflicts of interest?
Our sourcing prioritises non-commercial guideline bodies (NCI, ACMG, NCCN, NHGRI). Where we cite a manufacturer's technical specification — for instance saliva DNA yield from a self-collection kit — we label it as a vendor specification, not independent evidence.
Is anything here medical advice?
No. These are educational explainers. For any personal decision about testing, results, or risk, speak with a clinician or a certified genetic counsellor who can review your individual and family history.
- [1]JCO / PROMPT 2017. Balmaña J, Digiovanni L, Gaddam P, et al. Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing. J Clin Oncol.↗
- [2]ASCO 2016. Walsh MF, et al. Prospective Registry of Multiplex Testing (PROMPT): a web-based platform to assess cancer risk of genetic variants. ASCO Annual Meeting abstract 1518.↗
- [3]ACMG/AMP 2015. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: ACMG and AMP joint consensus recommendation. Genet Med.↗
- [4]MSK PROMPT. Memorial Sloan Kettering Cancer Center. Genetic Counseling and Genetic Testing for Hereditary Cancer: The PROMPT Study.↗
- [5]DNA Genotek / PMC3422993. Quality of DNA extracted from saliva samples collected with the Oragene self-collection kit; DNA Genotek OG-500 technical specification.↗
Start with the evidence, not the marketing
Every guide on this site follows the method above — sourced, qualified, and free of anything for sale. Explore the explainers, or read how variant classification actually works.