ABSTRACT (PRE/CO-CLINICAL SECTION) The Preclinical/Co-Clinical Section (PCS) provides a critical link between affected individuals and referring clinicians and the C-PAM. Guiding principles are 1) to maintain a dialog with affected individuals and referring clinicians to ensure that adequate information is available to prioritize creation of a model and to validate the model, and 2) to engage affected individuals and referring clinicians as partners, providing updates on progress in a responsible manner. We expect to receive nominations for creation of an animal model from several ongoing programs at UAB that have an existing queue of genomic variants for analysis, as well as from sources outside of UAB. The PCS will provide a secure web-based gateway for accession of clinical information, obtained with the informed consent of participants. The PCS team will review this information and summarize it in a PhenoTips entry. This in turn will be used to generate a Variant Phenopacket (VPP), which will include human phenotype ontology terms related to the affected individual's phenotype along with relevant genotypic information. There will also be the capacity to obtain and store biological samples, such as blood, urine, saliva, and surgical specimens, if needed. The VPP will be passed onto the Bioninformatics Section for further analysis, leading ultimately to information to guide a decision by the Steering Committee of whether to create a model. Once a model is made, the PCS will work together with the Disease Modeling Unit to provide co-clinical assessments. If the model is one that might demonstrate a phenotype similar to that seen in the affected individual, the PCS will help to validate the model phenotype in light of the clinical phenotype. Often this will require going back to the affected individual or referring clinician for additional phenotypic information. In other cases, the model will address cellular function altered by the genomic variant. Further validation of this finding might require additional studies in tissue obtained from the affected individual. The PCS will also work with the Disease Modeling Unit in studies of potential therapies. In some instances, a drug or substance might be identified that is recognized as having potential therapeutic benefit. In other instances, the creation of the model might enable a drug discovery effort. In either case, the PCS will work with the Disease Modeling Unit to assess potential therapies. If results shed light on the pathogenicity of a variant or on the availability of a possible treatment, these will be reviewed by a Clinical Curation Committee before any information is shared with the referring physician. Ultimately, if approved by the committee and the affected individual has opted into learning of such information, the PCS physician will communicate with the referring physician. Otherwise, general information on research progress will be maintained on the C-PAM portal to keep the affected individual and referring physician apprised of general progress.