{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T22:03:37Z","timestamp":1768255417296,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006400","name":"Alnylam Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006400","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a progressive and fatal disease with &gt;130 known underlying variants in the TTR gene. We describe the utility of two no-charge genetic testing programs in identifying TTR variants in participants across Europe\/Middle East and North America, respectively. Methods: Eligible adult participants in GeneAct\u00ae and Alnylam Act\u00ae had a family history or clinical suspicion of ATTRv. Testing was performed using gene panels for neuropathies or cardiomyopathy, or a single-gene TTR test. Diagnostic yield was defined as one pathogenic\/likely pathogenic variant in TTR. Results: Overall, 2713 and 89,760 participants were tested in GeneAct\u00ae and Alnylam Act\u00ae. Genetic diagnosis was established in 95 and 4297 participants, respectively, resulting in a diagnostic yield of 3.5% and 4.8%. V122I (p.V142I) was the most common variant, identified in 34 of these participants in GeneAct\u00ae and 3299 in Alnylam Act\u00ae. Cardiac and neurologic signs\/symptoms were the most common manifestations across both programs, as reflected in the specialties ordering tests in Alnylam Act\u00ae (cardiology, 29.1%; neurology, 31.5%). Conclusions: These data highlight the importance of genetic testing for early identification of ATTRv, especially among patients with cardiac and neuropathy symptoms. Genetic testing has the potential to improve diagnostic timeframes and outcomes in ATTRv.<\/jats:p>","DOI":"10.3390\/jcm14196821","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T12:33:03Z","timestamp":1758889983000},"page":"6821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness and Utility of Genetic Testing in Establishing a Diagnosis of Hereditary Transthyretin Amyloidosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5513-8352","authenticated-orcid":false,"given":"Akash","family":"Singh","sequence":"first","affiliation":[{"name":"Alnylam Pharmaceuticals, London SL6 1DA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3026-3595","authenticated-orcid":false,"given":"Marie","family":"Th\u00e9audin","sequence":"additional","affiliation":[{"name":"Service of Neurology, Neurosciences Department, Lausanne University Hospital (CHUV), University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-2994","authenticated-orcid":false,"given":"Chafic","family":"Karam","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6167-4512","authenticated-orcid":false,"given":"David","family":"Kasper","sequence":"additional","affiliation":[{"name":"ARCHIMED Life Science GmbH (ARCHIMEDlife), 1110 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berthold","family":"Streubel","sequence":"additional","affiliation":[{"name":"Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Frascello","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Bondue","sequence":"additional","affiliation":[{"name":"Department of Cardiology, H\u00f4pital Universitaire de Bruxelles, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41582-019-0210-4","article-title":"Hereditary transthyretin amyloidosis: A model of medical progress for a fatal disease","volume":"15","author":"Adams","year":"2019","journal-title":"Nat. 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