{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:06:36Z","timestamp":1792037196357,"version":"4.4.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The use of proactive genetic screening for disease prevention and early detection is not yet widespread. Professional practice guidelines from the American College of Medical Genetics and Genomics (ACMG) have encouraged reporting pathogenic variants that confer personal risk for actionable monogenic hereditary disorders, but only as secondary findings from exome or genome sequencing. The Centers for Disease Control and Prevention (CDC) recognizes the potential public health impact of three Tier 1 actionable disorders. Here, we report results of a large multi-center cohort study to determine the yield and potential value of screening healthy individuals for variants associated with a broad range of actionable monogenic disorders, outside the context of secondary findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible adults were offered a proactive genetic screening test by health care providers in a variety of clinical settings. The screening panel based on next-generation sequencing contained up to 147 genes associated with monogenic disorders within cancer, cardiovascular, and other important clinical areas. Sequence and intragenic copy number variants classified as pathogenic, likely pathogenic, pathogenic (low penetrance), or increased risk allele were considered clinically significant and reported. Results were analyzed by clinical area and severity\/burden of disease using chi-square tests without Yates\u2019 correction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 10,478 unrelated adults screened, 1619 (15.5%) had results indicating personal risk for an actionable monogenic disorder. In contrast, only 3.1 to 5.2% had clinically reportable variants in genes suggested by the ACMG version 2 secondary findings list to be examined during exome or genome sequencing, and 2% had reportable variants related to CDC Tier 1 conditions. Among patients, 649 (6.2%) were positive for a genotype associated with a disease of high severity\/burden, including hereditary cancer syndromes, cardiovascular disorders, or malignant hyperthermia susceptibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is one of the first real-world examples of specialists and primary care providers using genetic screening with a multi-gene panel to identify health risks in their patients. Nearly one in six individuals screened for variants associated with actionable monogenic disorders had clinically significant results. These findings provide a foundation for further studies to assess the role of genetic screening as part of regular medical care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-021-01999-2","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:04:21Z","timestamp":1629234261000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2126-0982","authenticated-orcid":false,"given":"Eden V.","family":"Haverfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D.","family":"Esplin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sienna J.","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Hatchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Ormond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Hanson-Kahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paldeep S.","family":"Atwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Macklin-Mantia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Hines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron W.-M.","family":"Sak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Bleyl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Hulick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ora K.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Velsher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Y. J.","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Weissman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Kruisselbrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Abel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Kettles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Slavotinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce A.","family":"Mendelsohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swaroop","family":"Aradhya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Nussbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"1999_CR1","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1038\/s41436-019-0502-5","volume":"21","author":"ACMG Board of Directors","year":"2019","unstructured":"ACMG Board of Directors. The use of ACMG secondary findings recommendations for general population screening: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2019;21:1467\u20138.","journal-title":"Genet Med"},{"key":"1999_CR2","doi-asserted-by":"publisher","unstructured":"Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013;15(7):565\u201374. https:\/\/doi.org\/10.1038\/gim.2013.73.","DOI":"10.1038\/gim.2013.73"},{"issue":"2","key":"1999_CR3","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/gim.2016.190","volume":"19","author":"SS Kalia","year":"2017","unstructured":"Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19(2):249\u201355. https:\/\/doi.org\/10.1038\/gim.2016.190.","journal-title":"Genet Med."},{"key":"1999_CR4","doi-asserted-by":"publisher","unstructured":"Olfson E, Cottrell CE, Davidson NO, Gurnett CA, Heusel JW, Stitziel NO, et al. Identification of medically actionable secondary findings in the 1000 Genomes. PLoS One. 2015;10(9):e0135193. https:\/\/doi.org\/10.1371\/journal.pone.0135193.","DOI":"10.1371\/journal.pone.0135193"},{"issue":"9","key":"1999_CR5","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/s41436-020-0810-9","volume":"22","author":"eMERGE Clinical Annotation Working Group","year":"2020","unstructured":"eMERGE Clinical Annotation Working Group. Frequency of genomic secondary findings among 21,915 eMERGE network participants. Genet Med. 2020;22(9):1470\u20137. https:\/\/doi.org\/10.1038\/s41436-020-0810-9.","journal-title":"Genet Med."},{"key":"1999_CR6","doi-asserted-by":"publisher","unstructured":"Hadar T, Mor P, Amit G, Lieberman S, Gekhtman D, Rabinovitch R, et al. Presymptomatic awareness of germline pathogenic BRCA variants and associated outcomes in women with breast cancer. JAMA Oncol. 2020;6(9):1460\u20133. https:\/\/doi.org\/10.1001\/jamaoncol.2020.2059.","DOI":"10.1001\/jamaoncol.2020.2059"},{"issue":"1","key":"1999_CR7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1146\/annurev-genom-083118-015253","volume":"21","author":"R Manchanda","year":"2020","unstructured":"Manchanda R, Lieberman S, Gaba F, Lahad A, Levy-Lahad E. Population screening for inherited predisposition to breast and ovarian cancer. Annu Rev Genomics Hum Genet. 2020;21(1):373\u2013412. https:\/\/doi.org\/10.1146\/annurev-genom-083118-015253.","journal-title":"Annu Rev Genomics Hum Genet."},{"key":"1999_CR8","unstructured":"Centers for Disease Control and Prevention (CDC), Office of Science and Office of Genomics and Precision Public Health. Tier 1 genomics applications and their importance to public health. In: Genomic application toolkit. Atlanta: CDC; 2014. https:\/\/www.cdc.gov\/genomics\/implementation\/toolkit\/tier1.htm. Accessed 13 Jan 2021."},{"issue":"6","key":"1999_CR9","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1159\/000341889","volume":"15","author":"MS Bowen","year":"2012","unstructured":"Bowen MS, Kolor K, Dotson WD, Ned RM, Khoury MJ. Public health action in genomics is now needed beyond newborn screening. Public Health Genomics. 2012;15(6):327\u201334. https:\/\/doi.org\/10.1159\/000341889.","journal-title":"Public Health Genomics."},{"issue":"9","key":"1999_CR10","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1038\/s41588-018-0202-0","volume":"50","author":"C Turnbull","year":"2018","unstructured":"Turnbull C, Sud A, Houlston RS. Cancer genetics, precision prevention and a call to action. Nat Genet. 2018;50(9):1212\u20138. https:\/\/doi.org\/10.1038\/s41588-018-0202-0.","journal-title":"Nat Genet."},{"key":"1999_CR11","doi-asserted-by":"publisher","unstructured":"Hu P, Dharmayat KI, Stevens CAT, Sharabiani MTA, Jones RS, Watts GF, et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis. Circulation. 2020;141(22):1742\u201359. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.119.044795.","DOI":"10.1161\/CIRCULATIONAHA.119.044795"},{"key":"1999_CR12","doi-asserted-by":"publisher","unstructured":"Ormondroyd E, Mackley MP, Blair E, Craft J, Knight JC, Taylor JC, et al. \u201cNot pathogenic until proven otherwise\u201d: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project. Genet Med. 2018;20(3):320\u20138. https:\/\/doi.org\/10.1038\/gim.2017.157.","DOI":"10.1038\/gim.2017.157"},{"issue":"3","key":"1999_CR13","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.ajhg.2018.07.009","volume":"103","author":"MLB Schwartz","year":"2018","unstructured":"Schwartz MLB, McCormick CZ, Lazzeri AL, Lindbuchler DM, Hallquist MLG, Manickam K, et al. A model for genome-first care: returning secondary genomic findings to participants and their healthcare providers in a large research cohort. Am J Hum Genet. 2018;103(3):328\u201337. https:\/\/doi.org\/10.1016\/j.ajhg.2018.07.009.","journal-title":"Am J Hum Genet"},{"key":"1999_CR14","doi-asserted-by":"publisher","unstructured":"Jamal L, Robinson JO, Christensen KD, Blumenthal-Barby J, Slashinski MJ, Perry DL, et al. When bins blur: patient perspectives on categories of results from clinical whole genome sequencing. AJOB Empir Bioeth. 2017;8(2):82\u20138. https:\/\/doi.org\/10.1080\/23294515.2017.1287786.","DOI":"10.1080\/23294515.2017.1287786"},{"key":"1999_CR15","doi-asserted-by":"publisher","unstructured":"Hart MR, Biesecker BB, Blout CL, Christensen KD, Amendola LM, Bergstrom KL, et al. Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study. Genet Med. 2019;21(5):1100\u201310. https:\/\/doi.org\/10.1038\/s41436-018-0308-x.","DOI":"10.1038\/s41436-018-0308-x"},{"key":"1999_CR16","volume-title":"NAM perspectives","author":"MF Murray","year":"2018","unstructured":"Murray MF, Evans JP, Angrist M, Chan K, Uhlmann WR, Doyle DL, et al. A proposed approach for implementing genomics-based screening programs for healthy adults. In: NAM perspectives. Washington, DC: National Academy of Medicine; 2018."},{"key":"1999_CR17","doi-asserted-by":"publisher","unstructured":"Webber EM, Hunter JE, Biesecker LG, Buchanan AH, Clarke EV, Currey E, et al. Evidence-based assessments of clinical actionability in the context of secondary findings: updates from ClinGen\u2019s Actionability Working Group. Hum Mutat. 2018;39(11):1677\u201385. https:\/\/doi.org\/10.1002\/humu.23631.","DOI":"10.1002\/humu.23631"},{"key":"1999_CR18","doi-asserted-by":"publisher","first-page":"aaf6814","DOI":"10.1126\/science.aaf6814","volume":"354","author":"FE Dewey","year":"2016","unstructured":"Dewey FE, Murray MF, Overton JD, Habegger L, Leader JB, Fetterolf SN, et al. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study. Science. 2016;354:aaf6814.","journal-title":"Science"},{"issue":"6","key":"1999_CR19","doi-asserted-by":"publisher","first-page":"500","DOI":"10.18043\/ncm.74.6.500","volume":"74","author":"AK Foreman","year":"2013","unstructured":"Foreman AK, Lee K, Evans JP. The NCGENES project: exploring the new world of genome sequencing. N C Med J. 2013;74(6):500\u20134. https:\/\/doi.org\/10.18043\/ncm.74.6.500.","journal-title":"N C Med J"},{"key":"1999_CR20","doi-asserted-by":"publisher","unstructured":"Truty R, Paul J, Kennemer M, Lincoln SE, Olivares E, Nussbaum RL, et al. Prevalence and properties of intragenic copy-number variation in Mendelian disease genes. Genet Med. 2019;21(1):114\u201323. https:\/\/doi.org\/10.1038\/s41436-018-0033-5.","DOI":"10.1038\/s41436-018-0033-5"},{"key":"1999_CR21","doi-asserted-by":"publisher","unstructured":"Lincoln SE, Truty R, Lin C-F, Zook JM, Paul J, Ramey VH, et al. A rigorous interlaboratory examination of the need to confirm next-generation sequencing-detected variants with an orthogonal method in clinical genetic testing. J Mol Diagn. 2019;21(2):318\u201389. https:\/\/doi.org\/10.1016\/j.jmoldx.2018.10.009.","DOI":"10.1016\/j.jmoldx.2018.10.009"},{"issue":"10","key":"1999_CR22","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1038\/gim.2017.37","volume":"19","author":"K Nykamp","year":"2017","unstructured":"Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho Y-Y, et al. Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Genet Med. 2017;19(10):1105\u201317. https:\/\/doi.org\/10.1038\/gim.2017.37.","journal-title":"Genet Med."},{"issue":"5","key":"1999_CR23","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med."},{"issue":"1","key":"1999_CR24","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1093\/ije\/dym159","volume":"37","author":"JP Ioannidis","year":"2008","unstructured":"Ioannidis JP, Boffetta P, Little J, O\u2019Brien TR, Uitterlinden AG, Vineis P, et al. Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008;37(1):120\u201332. https:\/\/doi.org\/10.1093\/ije\/dym159.","journal-title":"Int J Epidemiol."},{"issue":"8","key":"1999_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002631","volume":"15","author":"MJ Khoury","year":"2018","unstructured":"Khoury MJ, Feero WG, Chambers DA, Brody LC, Aziz N, Green RC, et al. A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health. PLoS Med. 2018;15(8):e1002631. https:\/\/doi.org\/10.1371\/journal.pmed.1002631.","journal-title":"PLoS Med."},{"issue":"6","key":"1999_CR26","doi-asserted-by":"publisher","first-page":"407","DOI":"10.7326\/M18-1722","volume":"169","author":"MF Murray","year":"2018","unstructured":"Murray MF. The path to routine genomic screening in health care. Ann Intern Med. 2018;169(6):407\u20138. https:\/\/doi.org\/10.7326\/M18-1722.","journal-title":"Ann Intern Med."},{"key":"1999_CR27","doi-asserted-by":"publisher","unstructured":"Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med. 2016;18(7):696\u2013704. https:\/\/doi.org\/10.1038\/gim.2015.148.","DOI":"10.1038\/gim.2015.148"},{"key":"1999_CR28","doi-asserted-by":"publisher","unstructured":"Amendola LM, Dorschner MO, Robertson PD, Salama JS, Hart R, Shirts BH, et al. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015;25(3):305\u201315. https:\/\/doi.org\/10.1101\/gr.183483.114.","DOI":"10.1101\/gr.183483.114"},{"issue":"1","key":"1999_CR29","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.1038\/s41467-018-05747-8","volume":"9","author":"P Natarajan","year":"2018","unstructured":"Natarajan P, Peloso GM, Zekavat SM, Montasser M, Ganna A, Chaffin M, et al. Deep-coverage whole genome sequences and blood lipids among 16,324 individuals. Nat Commun. 2018;9(1):3391. https:\/\/doi.org\/10.1038\/s41467-018-05747-8.","journal-title":"Nat Commun."},{"key":"1999_CR30","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1053\/j.gastro.2014.01.022","volume":"146","author":"AK Win","year":"2014","unstructured":"Win AK, Dowty JG, Cleary SP, Kim H, Buchanan DD, Young JP, et al. Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology. 2014;146:1208\u201311.e1-5.","journal-title":"Gastroenterology"},{"issue":"17","key":"1999_CR31","doi-asserted-by":"publisher","first-page":"3680","DOI":"10.1016\/j.ejca.2013.06.040","volume":"49","author":"B Boursi","year":"2013","unstructured":"Boursi B, Sella T, Liberman E, Shapiro S, David M, Kazanov D, et al. The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews. Eur J Cancer. 2013;49(17):3680\u20135. https:\/\/doi.org\/10.1016\/j.ejca.2013.06.040.","journal-title":"Eur J Cancer."},{"key":"1999_CR32","doi-asserted-by":"publisher","unstructured":"Liang J, Lin C, Hu F, Wang F, Zhu L, Yao X, et al. APC polymorphisms and the risk of colorectal neoplasia: a HuGE review and meta-analysis. Am J Epidemiol. 2013;177(11):1169\u201379. https:\/\/doi.org\/10.1093\/aje\/kws382.","DOI":"10.1093\/aje\/kws382"},{"issue":"4","key":"1999_CR33","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/gim.2016.19","volume":"18","author":"LG Biesecker","year":"2016","unstructured":"Biesecker LG. Overcalling secondary findings. Genet Med. 2016;18(4):416. https:\/\/doi.org\/10.1038\/gim.2016.19.","journal-title":"Genet Med."},{"key":"1999_CR34","doi-asserted-by":"publisher","unstructured":"Gupta S, Provenzale D, Llor X, Halverson AL, Grady W, Chung DC, et al. NCCN guidelines insights: genetic\/familial high-risk assessment: colorectal, version 2.2019. J Natl Compr Canc Netw. 2019;17(9):1032\u201341. https:\/\/doi.org\/10.6004\/jnccn.2019.0044.","DOI":"10.6004\/jnccn.2019.0044"},{"issue":"6","key":"1999_CR35","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/gim.2015.136","volume":"18","author":"MC Adams","year":"2016","unstructured":"Adams MC, Evans JP, Henderson GE, Berg JS. The promise and peril of genomic screening in the general population. Genet Med. 2016;18(6):593\u20139. https:\/\/doi.org\/10.1038\/gim.2015.136.","journal-title":"Genet Med."},{"issue":"3","key":"1999_CR36","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/s41436-019-0679-7","volume":"22","author":"PS Appelbaum","year":"2020","unstructured":"Appelbaum PS, Parens E, Berger SM, Chung WK, Burke W. Is there a duty to reinterpret genetic data? The ethical dimensions. Genet Med. 2020;22(3):633\u20139. https:\/\/doi.org\/10.1038\/s41436-019-0679-7.","journal-title":"Genet Med."},{"issue":"10","key":"1999_CR37","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1245\/s10434-018-6621-4","volume":"25","author":"S Yang","year":"2018","unstructured":"Yang S, Axilbund JE, O'Leary E, Michalski ST, Evans R, Lincoln SE, et al. Underdiagnosis of hereditary breast and ovarian cancer in Medicare patients: genetic testing criteria miss the mark. Ann Surg Oncol. 2018;25(10):2925\u201331. https:\/\/doi.org\/10.1245\/s10434-018-6621-4.","journal-title":"Ann Surg Oncol."},{"key":"1999_CR38","doi-asserted-by":"publisher","unstructured":"Sun L, Brentnall A, Patel S, Buist DSM, Bowles EJA, Evans DGR, et al. A cost-effectiveness analysis of multigene testing for all patients with breast cancer. JAMA Oncol. 2019;5(12):1718\u201330. https:\/\/doi.org\/10.1001\/jamaoncol.2019.3323.","DOI":"10.1001\/jamaoncol.2019.3323"},{"issue":"11","key":"1999_CR39","doi-asserted-by":"publisher","first-page":"e765","DOI":"10.1016\/j.amjmed.2019.03.012","volume":"132","author":"S Sorscher","year":"2019","unstructured":"Sorscher S. Universal multigene panel testing in all breast cancer patients. Am J Med. 2019;132(11):e765\u20136. https:\/\/doi.org\/10.1016\/j.amjmed.2019.03.012.","journal-title":"Am J Med."},{"key":"1999_CR40","doi-asserted-by":"publisher","unstructured":"Bastarache L, Hughey JJ, Hebbring S, Marlo J, Zhao W, Ho WT, et al. Phenotype risk scores identify patients with unrecognized Mendelian disease patterns. Science. 2018;359(6381):1233\u20139. https:\/\/doi.org\/10.1126\/science.aal4043.","DOI":"10.1126\/science.aal4043"},{"issue":"1","key":"1999_CR41","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.amepre.2010.09.027","volume":"40","author":"CA Bellcross","year":"2011","unstructured":"Bellcross CA, Kolor K, Goddard KAB, Coates RJ, Reyes M, Khoury MJ. Awareness and utilization of BRCA1\/2 testing among U.S. primary care physicians. Am J Prev Med. 2011;40(1):61\u20136. https:\/\/doi.org\/10.1016\/j.amepre.2010.09.027.","journal-title":"Am J Prev Med."},{"issue":"5","key":"1999_CR42","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2217\/pme-2018-0041","volume":"15","author":"KM Meagher","year":"2018","unstructured":"Meagher KM, Berg JS. Too much of a good thing? Overdiagnosis, or overestimating risk in preventive genomic screening. Per Med. 2018;15(5):343\u20136. https:\/\/doi.org\/10.2217\/pme-2018-0041.","journal-title":"Per Med."},{"key":"1999_CR43","doi-asserted-by":"crossref","unstructured":"Murray MF, Giovanni MA, Doyle DL, Harrison SM, Lyon E, Manickam K, et al. DNA-based screening and population health: a points to consider statement for programs and sponsoring organizations from the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021; online ahead of print.","DOI":"10.1038\/s41436-020-01082-w"},{"key":"1999_CR44","unstructured":"Bean LJH, Scheuner MT, Murray MF, Biesecker LG, Green RC, Monaghan KG, et al. A framework for understanding the current challenges and opportunities in genomic sequencing of apparently healthy individuals: a points to consider document from the ACMG. Genet Med. 2021; in press."},{"issue":"1","key":"1999_CR45","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/gim.2014.147","volume":"17","author":"H Hampel","year":"2015","unstructured":"Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70\u201387. https:\/\/doi.org\/10.1038\/gim.2014.147.","journal-title":"Genet Med."},{"key":"1999_CR46","doi-asserted-by":"crossref","unstructured":"Berliner JL, Cummings SA, Burnett BB, Ricker CN. Risk assessment and genetic counseling for hereditary breast and ovarian cancer syndromes \u2013 practice resource of the National Society of Genetic Counselors. J Genet Couns. 2021; online ahead of print.","DOI":"10.1002\/jgc4.1374"},{"issue":"1","key":"1999_CR47","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1002\/ajmg.c.31602","volume":"178","author":"K Stoll","year":"2018","unstructured":"Stoll K, Kubendran S, Cohen SA. The past, present and future of service delivery in genetic counseling: keeping up in the era of precision medicine. Am J Med Genet C Semin Med Genet. 2018;178(1):24\u201337. https:\/\/doi.org\/10.1002\/ajmg.c.31602.","journal-title":"Am J Med Genet C Semin Med Genet."},{"issue":"11","key":"1999_CR48","doi-asserted-by":"publisher","first-page":"435","DOI":"10.3390\/cancers10110435","volume":"10","author":"JA McCuaig","year":"2018","unstructured":"McCuaig JA, Armel SR, Care M, Volenik A, Kim RH, Metcalfe KA. Next-generation service delivery: a scoping review of patient outcomes associated with alternative models of genetic counseling and genetic testing for hereditary cancer. Cancers (Basel). 2018;10(11):435\u201371. https:\/\/doi.org\/10.3390\/cancers10110435.","journal-title":"Cancers (Basel)."}],"updated-by":[{"DOI":"10.1186\/s12916-021-02141-y","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000}}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-021-01999-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-021-01999-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-021-01999-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T09:04:37Z","timestamp":1635930277000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedicine.biomedcentral.com\/articles\/10.1186\/s12916-021-01999-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1999"],"URL":"https:\/\/doi.org\/10.1186\/s12916-021-01999-2","relation":{"has-review":[{"id-type":"doi","id":"10.32388\/2R5PIU","asserted-by":"object"}]},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]},"assertion":[{"value":"19 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s12916-021-02141-y","URL":"https:\/\/doi.org\/10.1186\/s12916-021-02141-y","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients provided informed consent (either written or verbal) before genetic screening tests were ordered. Relevant clinically reported variants and de-identified clinical information were collected for analyses with institutional review board approval (Western IRB, #20160282). The need for additional consent was waived.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"EVH, EDE, SJA, KEH, SA, and RLN are employees and stockholders of Invitae. SBB is an employee and stockholder of Genome Medical. LV receives a stipend from MedCan for her contributions as a medical advisor. RCG is a co-founder of Genome Medical and receives compensation for advising AIA, Grail, OptumLabs, Verily, and Wamburg. KEO, AH-K, PSA, SM-M, SH, CW-MS, ST, PJH, OKG, JYJG, SMW, TK, CA, MK, AS, and BAM declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"199"}}