One child in every 200 births may be affected by one of the approximately 6,000 monogenic diseases discovered so far. Establishing the pathogenicity of the mutations detected with NGS (Next-Generation Sequencing) techniques, within the sequence of the associated genes, will allow Precision Medicine concept to be developed. However, sometimes the clinical significance of the mutations detected in a genome may be uncertain (VUS, Variant of Uncertain Significance) which prevents the development of health measures devoted to personalize individuals' treatments. A VUS pathogenicity can be inferred thanks to evidences obtained from specific types of NGS studies. Therefore the union of supercomputing through HPC (High-Performance Computing) tools and the cloud computing paradigm (HPCC), within a Data Center federation environment offers a solution to develop and provide services to infer the pathogenicity of a set of VUS detected in a genome, while guaranteeing both the security of the information generated during the whole workflow and its availability.