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The functional impact of 1,570 individual amino acid substitutions in human OTC
Affiliation:1. Pacific Northwest Research Institute, Seattle, WA, USA;2. Department of Applied Mathematics, University of Washington, Seattle, WA, USA;3. Center for Genetic Medicine Research, Children’s National Research Institute, Children’s National Hospital, Washington, DC, USA;4. Department of Genomics and Precision Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA;5. Department of Neurology, Division of Neurogenetics and Neurodevelopmental Disabilities, Children’s National Hospital, Washington, DC, USA;6. Center for Neuroscience Research, Children’s National Research Institute, Children’s National Hospital, Washington, DC, USA;1. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;2. Department of Human Genetics, Katholieke Universiteit Leuven, ON4 Herestraat 49, 3000 Leuven, Belgium;3. Laboratory of Genetics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA;4. Columbia University, New York, NY 10027, USA;5. Genentech, San Francisco, CA 94080, USA;6. Mayo Clinic, Rochester, MN 55902, USA;7. Children’s Hospital of Pennsylvania, Philadelphia, PA 19104, USA;8. Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;9. Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;10. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, P.R. China;2. Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, P.R. China;1. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA;2. Division of Laboratory Services, Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA;3. Association of Public Health Laboratories, Silver Spring, MD, USA;4. Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA;5. Center for Public Health Innovation, CI International, Littleton, CO, USA;1. Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA;2. Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA;3. Section of Hematology & Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA;1. Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA;2. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;3. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA;4. VA Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA CT Healthcare System, West Haven, CT, USA;5. Department of Anthropology, University of Toronto, Mississauga, ON, Canada;6. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada;7. Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;8. Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA;9. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27705, USA;10. VA Cooperative Studies Program Epidemiology Center-Durham, Department of Veterans Affairs, Durham, NC 27705, USA;11. Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA;12. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA;1. Rady Children’s Institute for Genomic Medicine, San Diego, CA 92123, USA;2. Rady Children’s Hospital, San Diego, CA 92123, USA;3. Keck Graduate Institute, Claremont, CA 91711, USA;4. Illumina, Inc., San Diego, CA 92122, USA;5. Alexion, Astra Zeneca Rare Disease, Boston, MA 02210, USA;6. Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA;7. Fabric Genomics, Inc., Oakland, CA 94612, USA;8. Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School, Boston, MA 02115, USA;9. Genomenon, Inc., Ann Arbor, MI 48108, USA;10. TileDB, Inc., Cambridge, MA 02142, USA;11. Luna PBC, Inc., San Diego, CA 92121, USA
Abstract:
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  • Keywords:model organisms  rare variants  SNV analysis/discovery  metabolic disorder  X-linked disease  Oxford Nanopore sequencing  urea cycle disorder  OTC deficiency  multiplexed assays of variant effect  variant interpretation  rare disease
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