Project Summary/Abstract Advances in genomic sequencing and analysis techniques have enabled the molecular diagnosis of many individuals and families with rare disease. Finding these diagnoses may pave the way to better treatments or even cures, in addition to decreasing stress and empowering medical decision-making. However, access to genomic sequencing has not been equitable which has led to poor understanding of the genomic landscape of rare diseases and of the potential benefit of genomic medicine in addition to limited insight into factors necessary consider in increasing access. The Rare Genomes Project (RGP) was established at the Broad Institute in order to facilitate genetic diagnosis using genome sequencing for individuals and families with rare disease and has resulted in many diagnoses involving both established and novel disease genes. Though RGP does allow for more access to genome sequencing than would otherwise be possible through clinical routes, the RGP study participants have been overwhelmingly white, well-resourced, and with high educational and household income status. This project seeks to further expand access to genome sequencing through RGP to historically underserved and/or minoritized populations in an innovative approach that directly targets barriers identified through our theoretical framework in order to identify diagnoses for a diverse group of participants with rare disease (Aim 1). We will also gain critical insight into the process and context of implementing genomic medicine in underserved populations using outcomes measures derived from our conceptual framework (Aim 2). Finally, we will also examine motivations for pursuing genome sequencing and the impact of a genetic diagnosis in underserved/minoritized populations (Aim 3). Taken together, these results will inform future equitable approaches to incorporate genomic medicine into clinical practice.