The invention relates to the field of personalized medicine, and the ability to administer targeted therapies consequently to biomarkers functional identification. In particular, the invention relates to the field of clinical applicable methods for the characterization, and especially the functional evaluation, of genetic variants in a patient. In particular, the invention relates to the field of the characterization, and classification, of variants of uncertain significance (VUS) or other unreported variants in patients. The in vitro method presented here is effective for the characterization of the functional impact of genetic variants in a patient, in particular of VUS, such as BRCA1 and BRCA2 VUS. The inventors have shown that this experimental framework can be used to obtain the necessary biological evidence of VUS function required for the prescription of targeted treatment within three weeks, which is compatible with use in clinical application.