A VUS is a genetic variant identified through a genetic test for which, at the time of analysis, there is not enough scientific evidence to determine whether it is benign or associated with a clinical condition (pathogenic/likely pathogenic). In other words, it is an “uncertain” result: it does not confirm a diagnosis and cannot support definitive clinical decisions.

No. A VUS is not a conclusive result. It simply means that, at the time it was identified, the scientific community did not have enough evidence to determine its clinical significance.

Because genetics is a continuously evolving field: new studies are published, databases are updated, new clinical cases emerge, and biological mechanisms become clearer. As a result, what is uncertain today may become clearer in the future.

It involves systematically assessing whether new evidence has emerged since your report was issued that could change the clinical interpretation of the variant. Rather than a one-time process, it is most valuable when performed continuously and with full traceability.

Reanalysis typically involves reprocessing genetic data using updated pipelines and/or expanding the analysis, for example to additional genes, regions, or approaches. This usually applies to whole exome sequencing (WES) or whole genome sequencing (WGS) data. Re-evaluation, on the other hand, focuses on an already identified variant and answers a specific question: “Is there now enough scientific evidence to interpret this variant better than before?” RE-SOLVE is primarily designed for this second need.

If the classification changes, for example to “pathogenic” or “benign”, the update is documented and communicated promptly, so that your clinician can assess its potential implications for you and, if relevant, your family members.