PROJECT SUMMARY/ABSTRACT We propose to continue and improve the Intermountain West Clinical Site at the University of Utah for the Undiagnosed Disease Network. The site will continue to provide unprecedented access to a vast area across states that encompasses ~10% of the Continental US. Residents in the Intermountain West in particular are among the most underserved in the United States; with rural, minority, and low-income groups historically 'genetically underserved', including a large Native American population. As we enroll and evaluate a minimum of 15 participants / families, we will focus on increasing equity by intentionally supporting and promoting the enrollment of participants from underserved, minority, and economically disadvantages communities. While we will aim to evaluate participants with disorders from any specialty, we will leverage our specific expertise in genetics, dysmorphology, biochemical genetics and metabolism, bone and cartilage disorders, endocrinology, immunology, vascular anomalies, neurology and neuromuscular disease. With the goal of increasing value, we will streamline operations to improve quality while reducing costs, as an important step towards sustainability. To further support the transition of the UDN and our clinical site to a sustainable resource, we will develop further our internal and external sustainability plans. Internally, we will continue to improve our already successful program of a) increasing operational efficiencies to decrease costs by a combination of streamlined operations, remote visits, and partnerships; and b) combining clinical billing, institutional support, and philanthropy to support diagnostic evaluations, especially those for underserved and economically disadvantaged participants. Externally, to promote sustainability of the UDN as a national resource, we will share our processes and tools and continue to work with our bioinformatics team to bring to the UDN innovative bioinformatics tools to advance the power and the reach of genomic discovery, including IOBIO and CALYPSO. In summary, the Intermountain West Clinical Site will bring together the team, experience, resources, and institutional support to advance the shared goal of UDN – improve the diagnosis and management of difficult- to-diagnose and new diseases—efficiently and equitably, strongly supporting the transition of the UDN to a sustainable national resource.

PROJECT NARRATIVE The Intermountain West Clinical Site of the Undiagnosed Disease Network will continue to help adults and children with undiagnosed diseases spread across ~10% of the Continental US get access to unprecedented diagnostic and care resources through team science and innovative genetic tools. The overall goals are to promote equity by improving recruitment of families from underserved, minority, and economically disadvantaged communities; streamline operations to improve efficiencies and value; and increase sustainability of the clinical site as well as the UDN.