{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:57:17Z","timestamp":1791482237792,"version":"4.3.4"},"reference-count":109,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6787","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,2,19]]},"abstract":"<jats:p>\n                    Variants in the familial hypercholesterolemia gene\n                    <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n                    \u2014the most important genetic driver of cardiovascular disease\u2014can raise circulating low-density lipoprotein (LDL) cholesterol concentrations and increase the risk of premature atherosclerosis. Definitive classifications are lacking for nearly half of clinically encountered\n                    <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n                    missense variants, limiting interventions that reduce disease burden. We tested the impact of ~17,000 (nearly all possible)\n                    <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n                    coding variants on both LDLR cell-surface abundance and LDL uptake, yielding sequence\u2013function maps that recapitulate known biochemistry, offer functional insights, and provide evidence for interpreting clinical variants. Functional scores correlated with hyperlipidemia phenotypes in prospective human cohorts and augmented polygenic scores to improve risk inference, highlighting the potential of this resource to accelerate familial hypercholesterolemia diagnosis and improve patient outcomes.\n                  <\/jats:p>","DOI":"10.1126\/science.ady7186","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:59:14Z","timestamp":1761847154000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["The functional landscape of coding variation in the familial hypercholesterolemia gene\n                    <i>LDLR<\/i>"],"prefix":"10.1126","volume":"391","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5480-7733","authenticated-orcid":true,"given":"Daniel R.","family":"Tabet","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0340-9325","authenticated-orcid":true,"given":"Atina G.","family":"Cot\u00e9","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2697-3762","authenticated-orcid":true,"given":"Megan C.","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA."},{"name":"Division of Cardiovascular Medicine, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1628-9390","authenticated-orcid":true,"given":"Jochen","family":"Weile","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashyad","family":"Rayhan","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iosifina","family":"Fotiadou","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishka","family":"Kishore","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roujia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3554-0464","authenticated-orcid":true,"given":"Da","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-4686","authenticated-orcid":true,"given":"Jennifer J.","family":"Knapp","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela S.","family":"Carrero","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5034-7811","authenticated-orcid":true,"given":"Olivia","family":"Taverniti","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5844-4367","authenticated-orcid":true,"given":"Anna","family":"Axakova","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5834-0620","authenticated-orcid":true,"given":"Jack M. P.","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-7388","authenticated-orcid":true,"given":"Mohammad M.","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Sowlati-Hashjin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-3438","authenticated-orcid":true,"given":"Aanshi","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranim","family":"Maaieh","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-6532","authenticated-orcid":true,"given":"Michael","family":"Garton","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9149-551X","authenticated-orcid":true,"given":"Kenneth","family":"Matreyek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-1713","authenticated-orcid":true,"given":"Douglas M.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Departments of Genome Sciences and Bioengineering, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-3799","authenticated-orcid":true,"given":"Mafalda","family":"Bourbon","sequence":"additional","affiliation":[{"name":"BioISI, Biosystems &amp; Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade de Lisboa, Lisboa, Portugal."},{"name":"Grupo De Investiga\u00e7\u00e3o Cardiovascular, Unidade I&amp;d, Departamento De Promo\u00e7\u00e3o Da Sa\u00fade E Doen\u00e7as N\u00e3o Transmiss\u00edveis, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Lisboa, Portugal."},{"name":"Centro Cardiovascular da Universidade de Lisboa, CCUL (CCUL@RISE), C.A.M.L, Faculdade de Medicina, Universidade de Lisboa, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5606-2102","authenticated-orcid":true,"given":"Simon G.","family":"Pfisterer","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-4713","authenticated-orcid":true,"given":"Andrew M.","family":"Glazer","sequence":"additional","affiliation":[{"name":"Department of Medicine (Genomic Medicine and Clinical Pharmacology), Vanderbilt University Medical Center, Nashville, TN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett M.","family":"Kroncke","sequence":"additional","affiliation":[{"name":"Department of Medicine (Genomic Medicine and Clinical Pharmacology), Vanderbilt University Medical Center, Nashville, TN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria N.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Stanford Center for Inherited Cardiovascular Disease, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-9577","authenticated-orcid":true,"given":"Euan A.","family":"Ashley","sequence":"additional","affiliation":[{"name":"Stanford Center for Inherited Cardiovascular Disease, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua W.","family":"Knowles","sequence":"additional","affiliation":[{"name":"Stanford Center for Inherited Cardiovascular Disease, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Division of Cardiovascular Medicine and Cardiovascular Institute, Department of Medicine, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2450-736X","authenticated-orcid":true,"given":"Melina","family":"Claussnitzer","sequence":"additional","affiliation":[{"name":"The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Center for Genomic Medicine and Endocrine Division, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Department of Medicine, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-2809","authenticated-orcid":true,"given":"Elizabeth T.","family":"Cirulli","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":true,"given":"Robert A.","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Medicine and Robarts Research Institute, Western University, London, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-0389","authenticated-orcid":true,"given":"Dan M.","family":"Roden","sequence":"additional","affiliation":[{"name":"Department of Medicine (Genomic Medicine and Clinical Pharmacology), Vanderbilt University Medical Center, Nashville, TN, USA."},{"name":"Departments of Pharmacology and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5181-2664","authenticated-orcid":true,"given":"Calum A.","family":"MacRae","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA, USA."},{"name":"Divisions of Cardiovascular Medicine and Genetics, Department of Medicine, MassGeneral Brigham, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6628-649X","authenticated-orcid":true,"given":"Frederick P.","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada."},{"name":"Donnelly Centre, University of Toronto, Toronto, ON, Canada."},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada."},{"name":"Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2018.09.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000297"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.174194"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078124"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.044"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.520"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.121.003501"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03587-X"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.8543"},{"key":"e_1_3_3_12_2","unstructured":"Centers for Disease Control and Prevention (CDC) Tier 1 Genomics Applications and their Importance to Public Health (2014); https:\/\/archive.cdc.gov\/www_cdc_gov\/genomics\/implementation\/toolkit\/tier1.htm."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23634"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01726-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2024.10.006"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004855"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2022.04.005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2023.03.013"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.06.001"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-018-1916-x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.09.007"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-072920-032107"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.93"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3791\/58564"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx183"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4582"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki387"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1809937"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2007.08.017"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133354"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)37702-0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)88240-4"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08223-0"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900194200"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39742-X"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2021.09.012"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0690-2"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.210"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.122.003792"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.08.012"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1563"},{"key":"e_1_3_3_47_2","volume-title":"Familial hypercholesterolemia: Report of a second WHO Consultation","author":"World Health Organization","year":"1999","unstructured":"World Health Organization, Familial hypercholesterolemia: Report of a second WHO Consultation (WHO, 1999)."},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S176853"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2016.08.001"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.070982"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901073400103"},{"key":"e_1_3_3_52_2","doi-asserted-by":"crossref","unstructured":"D. J. Thompson D. Wells S. Selzam I. Peneva R. Moore K. Sharp W. A. Tarran E. J. Beard F. Riveros-Mckay C. Giner-Delgado D. Palmer P. Seth J. Harrison M. Futema G. McVean V. Plagnol P. Donnelly M. E. Weale Genomics England Research Consortium UK Biobank release and systematic evaluation of optimised polygenic risk scores for 53 diseases and quantitative traits bioRxiv 2022.06.16.22276246 [Preprint] (2022); .10.1101\/2022.06.16.22276246","DOI":"10.1101\/2022.06.16.22276246"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0183-z"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17374-3"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2025.01.004"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.320287"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02796-z"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001381"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjco.2024.08.005"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20230918"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168974"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00005"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2011.04.003"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2023.2176753"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-024-01392-7"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59959"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11558"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11526-w"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.032"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.015"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.12.002"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008862"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0461-z"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.07.016"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.115.175802"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0968-2"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010739"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.01.019"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08349-1"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010940"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16141-8"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.12.003"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1151"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3700"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00722"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02935-8"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002786"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2020.05.041"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.069828"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-024-01340-5"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02986-x"},{"key":"e_1_3_3_93_2","unstructured":"D. Fowler D. Adams N. Ahituv C. Bock B. Bolognesi S. Chanock J. Cheng J. Cho M. Davis G. del Angel J. Doench J. Ellingford K. Estrada K. Kyle Fahr S. Fayer I. Gallego Romero A. Glazer D. Huangfu M. Landrum B. Lehner A. Lossie M.-J. Martin M. Massart S. Nelson A. O\u2019Donnell-Luria V. Parikh T. Pesaran J. Posey B. Powell D. Roden A. Rubin R. K. Semple D. Simola H. Singh L. Starita M. Tejura J. Vockley A. Wagner H. Won E. Birney J. Cool M. Hurles C. Hutter L. Muffley H. L. Rehm F. Roth Atlas of Variant Effects 2030 Roadmap: resolving human variants of uncertain significance Version V1 Zenodo (2025); https:\/\/doi.org\/10.5281\/ZENODO.15420414."},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-025-01201-7"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1638"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.143"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1534\/g3.117.041277"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2025.08.019"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20177908"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01435-7"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae182"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-0711-1"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx655"},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac074"},{"key":"e_1_3_3_106_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-024-03314-7"},{"key":"e_1_3_3_107_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00885-0"},{"key":"e_1_3_3_108_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00757-z"},{"key":"e_1_3_3_109_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03252-6"},{"key":"e_1_3_3_110_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2025.101011"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.ady7186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:03:12Z","timestamp":1776700992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.ady7186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":109,"journal-issue":{"issue":"6787","published-print":{"date-parts":[[2026,2,19]]}},"alternative-id":["10.1126\/science.ady7186"],"URL":"https:\/\/doi.org\/10.1126\/science.ady7186","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"2025-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eady7186"}}