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Precision medicine, defined as a new model of patient-powered research that will give clinicians the ability to select the best treatment for an individual patient, holds the key that will allow health IT to merge advances in genomics research with new methods for managing and analyzing large data sets. This will accelerate research and biomedical discoveries. However, clinical improvements are often designed to reduce variation. So, how do systems balance tailoring medicine to each patient with standardizing care? The answer is precise registries. For example, using registries that can account for the most accurate, specific patients and disease, clinicians can use gene variant knowledge bases to provide personalized care.