{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:45:17Z","timestamp":1791942317717,"version":"4.3.4"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"27","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL164560"],"award-info":[{"award-number":["HL164560"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR081941"],"award-info":[{"award-number":["AR081941"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K08HL164885"],"award-info":[{"award-number":["K08HL164885"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["BBC\/F\/21\/220106"],"award-info":[{"award-number":["BBC\/F\/21\/220106"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NSF","award":["EEC-1647837"],"award-info":[{"award-number":["EEC-1647837"]}]},{"name":"The British Heart Foundation\u2019s Big Beat Challenge award to CureHeart","award":["BBC\/F\/21\/220106"],"award-info":[{"award-number":["BBC\/F\/21\/220106"]}]},{"name":"NSF (NSF) Engineering Research Center on Cellular Metamaterials","award":["EEC-1647837"],"award-info":[{"award-number":["EEC-1647837"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:p>\n                    Hypertrophic cardiomyopathy (HCM) variants in genes encoding the myosin heavy chain (MHC) (\n                    <jats:italic toggle=\"yes\">MYH7<\/jats:italic>\n                    ), myosin light chains (\n                    <jats:italic toggle=\"yes\">MYL2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">MYL3<\/jats:italic>\n                    ), and cardiac myosin binding protein-C (cMyBP-C,\n                    <jats:italic toggle=\"yes\">MYBPC3<\/jats:italic>\n                    ) lead to cardiac hypertrophy, with abnormal contractility, relaxation, and energy consumption. Here, we defined the structural consequences of pathogenic and benign missense variants in these genes by mapping 233 variants (\n                    <jats:italic toggle=\"yes\">MYH7<\/jats:italic>\n                    , n = 175;\n                    <jats:italic toggle=\"yes\">MYBPC3<\/jats:italic>\n                    , n = 41;\n                    <jats:italic toggle=\"yes\">MYL2<\/jats:italic>\n                    , n = 12;\n                    <jats:italic toggle=\"yes\">MYL3<\/jats:italic>\n                    , n = 5) onto a cryo-EM-based atomic model of the human cardiac thick filament. We identified HCM variants residing in 30 molecular interfaces of the complex thick filament interactome, including the two main interfaces of the myosin interacting-heads motif (IHM), and interfaces involving the MHC, essential and regulatory light chains, and cMyBP-C. None of the 21 variants classified as benign were within interfaces. We demonstrated earlier disease onset and adverse outcomes in HCM patients with pathogenic variants within vs. outside of molecular interfaces, emphasizing their importance in normal thick filament function and improving risk stratification of patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2529234123","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:11:41Z","timestamp":1782760301000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Thick filament molecular interfaces play a critical role in the pathogenesis of hypertrophic cardiomyopathy"],"prefix":"10.1073","volume":"123","author":[{"given":"Debabrata","family":"Dutta","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Cell Biology and Imaging, Department of Radiology, University of Massachusetts Chan Medical 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