Alberta patients with or suspected of having rare genetic diseases continue to face lengthy diagnostic odysseys, and clinical genome wide sequencing has emerged as a rapid and cost-effective approach to diagnosis. Large scale clinical genomics are not available in Alberta, and Alberta Precision Laboratories (APL) has relied primarily on US commercial labs to provide clinical genome-wide sequencing (GWS) at significant and increasing cost. This project proposes to address whether all or most costs could be offset by implementation of clinical GWS in Alberta, as well as addressing concerns associated with reliance of non-Canadian providers (i.e. availability of data for re-analysis and secondary uses, privacy and legal concerns). The project proposes to transform the care of patients with rare disease by optimizing clinical workflows, building clinical genomics capacity, driving the implementation of clinical GWS, integrating genomic data in Alberta and Canada, while also evaluating the effectiveness of in-house GWS to support evidence-informed adoption and de-adoption decisions.