• Lorelei A Bandel, Robert A Vierkant, Teresa M Kruisselbrink, Michelle L Bublitz, Tammy A Wilson, Sebastian M Armasu, Jan B Egan, Richard J Presutti, Niloy Jewel J Samadder, Aleksandar Sekulic, Rory J Olson, Jennifer Tan-Arroyo, Joel A Morales-Rosado, Eric W Klee, Matthew J Ferber, Jennifer L Kemppainen, Jennifer L Anderson, Jessa S Bidwell, Joseph J Wick, Victor E Ortega, William V Bobo, Pavel N Pichurin, Jessica M Mcmillan, DeAnna M Weaver, Douglas L Riegert-Johnson, Alanna M Cera, Lauren M Boucher, Iftikhar J Kullo, Sarah K Mantia, Matthew T Jones, Nicholas B Larson, Tony C Luehrs, Jon W Leitzke, Hugues Sicotte, Shulan Tian, Jennifer R Stavlund, Joel E Pacyna, Richard R Sharp, Akwasi A Asabere, James Lu, Tammy M McAllister, T'Nita S Walker, A Keith Stewart, Gianrico Farrugia, and Konstantinos N Lazaridis.
• Center for Individualized Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA.
• Mayo Clin. Proc. 2024 Nov 5.

ObjectiveTo execute a large-scale, decentralized, clinical-grade whole exome sequencing study, coined Tapestry, for clinical practice, research discovery, and genomic education.Patients And MethodsBetween July 1, 2020, and May 31, 2024, we invited 1,287,608 adult Mayo Clinic patients to participate in Tapestry. Of those contacted, 114,673 patients were consented and 98,222 (65.2% women) are currently enrolled: 62,495 (63.6%) were recruited from Minnesota-, 18,353 (18.7%) from Florida- and 17,374 (17.7%) from Arizona-based practices. Saliva from participants was used to extract DNA, and whole exome sequencing plus ∼300,000 single nucleotide polymorphisms (ie, Exome+ assay) were sequenced by a clinical lab. Results for the Centers for Disease Control and Prevention Tier 1 genes (eg, hereditary breast, ovarian cancer syndrome: BRCA1/2; Lynch syndrome: MLH1, MSH2, MSH6, PMS2, and EPCAM; and familial hypercholesterolemia: APOB, LDLR, PCSK9, and LDLRAP1) were interpreted and entered into the electronic health record.ResultsThe median age of participants was 59.1 years and ∼11% were from racial/ethnic groups under-represented in research. One thousand eight hundred nineteen (1.9%) participants had actionable pathogenic or likely pathogenic variants (50.0% BRCA1/2, 28.4% familial hypercholesterolemia, and 22.2% Lynch syndrome). Positive results were communicated by genetic counselors who educated patients and providers. Thus far, 62,758 patients' Exome+ assays are stored for research, and the Tapestry Data Access Committee has received 118 requests from investigators, of which 82 have been approved, resulting in the delivery of 1,117,410 Exome+ assays to researchers.ConclusionA large, decentralized, clinical Exome+ assay study in a tertiary medical center detects actionable germline variants, educates patients as well as providers, and offers access to big data for discovery that advances human health.Trial Registrationclinicaltrials.gov Identifier: NCT05212428.Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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