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We are delighted to welcome you to the 2019 edition of the Human Genetics and Genomics Gordon conference, a tradition that started in 1995 and continues strong. We will be coming together in an idyllic setting to take stock of the field as it continues to grow apace and to imagine where we are headed. There is no question that Human Genetics is at a proverbial crossroads, pulled in three overlapping, but sometimes competing directions: 1) the ever-increasing acquisition of genetic/genomic data, sometimes but not always accompanied by phenotypic information; 2) the pressing need to interpret variation at the level of allele, gene, macromolecular complex, and signaling cascade; and 3) the delivery of relevant data to the clinic to potentiate medical decisions and to develop therapeutics. The nexus of these three pivotal questions will be the focus of our conference. In the celebrated tradition of the Gordon Research Conferences, we look forward to welcoming both leaders of our field and neophytes, from academia and industry, to debate, openly and vigorously, the questions that define our time in genetics. At the end of our week, we hope to have learned from each other, to have challenged our respective preconceived notions and adages, and to have found a modicum of directionality that will help inform the design of our future endeavors.