PROMPT — the Prospective Registry Of MultiPlex Testing

PROMPT — the Prospective Registry Of MultiPlex Testing — was a real online research registry launched in September 2014, after panel sequencing made it possible to interrogate many cancer-susceptibility genes at once. It was a multi-institution collaboration whose partners included Memorial Sloan Kettering Cancer Center (MSKCC), the University of Pennsylvania (Penn), the Mayo Clinic and others, working alongside commercial laboratories and the advocacy community.

Its purpose was narrow and useful: gather families carrying alterations in the less-characterised genes — beyond BRCA1/BRCA2 and the Lynch-syndrome genes — so that penetrance (real-world cancer risk) could be estimated for genes such as ATM, CHEK2, PALB2, BARD1, BRIP1, NBN, RAD51C and RAD51D.

We honour PROMPT here as heritage. This site is an educational explainer that builds on its citation record; it is not the original registry and makes no claim that PROMPT is currently enrolling participants.

A registry pools individual results into one prospective dataset so that questions no single clinic could answer become tractable. The pressing question in 2014 was the variant of uncertain significance (VUS): a DNA change whose effect on cancer risk is, on current evidence, unknown — neither confidently pathogenic nor confidently benign under the ACMG/AMP five-tier framework (Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign).

The more genes a panel reads, the more VUS it surfaces. Reported figures show the prevalence climbing from roughly 6% for BRCA1/BRCA2 alone, to about 14% when fewer than ten extra genes are added, and to roughly 32% once more than ten additional genes are included. A registry that follows families over time is one of the few ways to move a variant out of that uncertain middle tier.