{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:53:24Z","timestamp":1790934804383,"version":"4.1.0"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Mainstream cardiac genetic testing, in which the treating cardiologist orders and returns multigene panel results without a traditional genetic counseling session, may expand access, but no mainstream program has quantified the operational burden. We quantified high-risk genotypes, variant reclassification, and carrier findings in a mainstream cardiomyopathy testing program to characterize the infrastructure required for safe scale-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We retrospectively analyzed 482 consecutive patients with dilated cardiomyopathy (n=338), nondilated left ventricular cardiomyopathy (n=84), or hypertrophic cardiomyopathy (n=60) who underwent multigene panel testing ordered by cardiologists at the Broderick Cardiomyopathy Program (January 2022 to February 2026). Variant classifications used each laboratory\u2019s most current interpretation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Diagnostic pathogenic\/likely pathogenic variants were identified in 95 of 482 patients (yield, 19.7% [95% CI, 16.4%\u201323.5%]) across 21 genes. Three categories of results required program-level infrastructure: (1) 18 of 95 genotype-positive patients (18.9%) had high-risk genotypes (\n                      <jats:italic toggle=\"yes\">DSP<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">LMNA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">FLNC<\/jats:italic>\n                      [truncating],\n                      <jats:italic toggle=\"yes\">RBM20<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DES<\/jats:italic>\n                      ) requiring genotype-specific management; (2) 8 of 12 reclassified variants (12\/743 total, 1.6%) crossed the pathogenic\/likely pathogenic threshold, including 7 variant of uncertain significance-to- pathogenic\/likely pathogenic upgrades converting nondiagnostic patients to genotype-positive; and (3) carrier findings comprised 26 of 121 pathogenic\/likely pathogenic variants (21.5%), inflating apparent yield to 23.7% if carrier findings were not distinguished from diagnostic results based on gene inheritance pattern. Variants of uncertain significance were reported in 295 patients (61.2%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These data identify 5 capabilities that support safe mainstream scale-up: high-risk genotype pathways for the 1 in 5 diagnostic patients with a high-risk variant, variant surveillance with recontact capacity for the 1 in 60 patients affected by actionable reclassification, recognition of gene inheritance pattern for the 1 in 19 patients with a carrier finding, a defined referral pathway to medical genetics, and standardized family screening infrastructure for all result categories.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.126.005782","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:00:10Z","timestamp":1790931610000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiologist-Delivered Genetic Testing in 482 Patients With Cardiomyopathy: The Infrastructure Needed for Mainstream Testing at Scale"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9556-1350","authenticated-orcid":true,"given":"Omid","family":"Kiamanesh","sequence":"first","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-3049","authenticated-orcid":true,"given":"Susan","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-2433","authenticated-orcid":true,"given":"Robert","family":"Miller","sequence":"additional","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Lyons","sequence":"additional","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0535-9771","authenticated-orcid":true,"given":"Jonathan","family":"Howlett","sequence":"additional","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4921-0802","authenticated-orcid":true,"given":"Lea","family":"Harper","sequence":"additional","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8195-8411","authenticated-orcid":true,"given":"Lauren","family":"Archer","sequence":"additional","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5646-6745","authenticated-orcid":true,"given":"Noelle","family":"Mahon","sequence":"additional","affiliation":[{"name":"Broderick Cardiomyopathy Program, Libin Cardiovascular Institute, University of Calgary, Canada (O.K., R.M., K.L., J.H., L.H., L.A., N.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2534-8273","authenticated-orcid":true,"given":"Julien","family":"Marcadier","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Alberta Health Services, Calgary, Canada (J.M., K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-8942","authenticated-orcid":true,"given":"Kim","family":"McBride","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Alberta Health Services, Calgary, Canada (J.M., 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