To accelerate the pace of Mendelian disease gene discovery and clinical implementation, we created a Pediatric Mendelian Genomics Research Center (MGRC), leveraging the broad pediatric clinical and research expertise and expertise in providing comprehensive and affordable genetic testing. Our Center unites world class experts combining basic and translational research with innovative approaches to phenotyping, variant identification and functional investigation of both coding and non-coding sequence changes with the goals of discovering novel Mendelian gene variations and identifying variants not detected on current sequencing pipelines, disambiguating uncertain variants into disease-causing versus benign categorizations, and sharing information by working collaboratively with the MGRC community.