{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:49:09Z","timestamp":1787500149320,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CUTTIN22XX0"],"award-info":[{"award-number":["CUTTIN22XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Genetic Counseling"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Variants in the cystic fibrosis transmembrane conductance regulator (\n                    <jats:italic>CFTR<\/jats:italic>\n                    ) gene, which causes cystic fibrosis, have become increasingly well\u2010characterized in recent decades. However, clinicians remain challenged by\n                    <jats:italic>CFTR<\/jats:italic>\n                    variants that result in variable expressivity and reduced penetrance, including the variant R117H (c.350G&gt;A) and the intron 9 poly\u2010thymidine (poly\u2010T) and poly\u2010thymidine\u2010guanosine (TG) tracts, highlighting a knowledge gap that impacts the delivery of accurate information to patients and families. To address this gap, we developed an educational resource that provides descriptive likelihoods of specific phenotypes that may result from genotypes including R117H and the poly\u2010T and TG tracts. Development of the resource was grounded in an extensive literature review, clinical expertise, and publicly available\n                    <jats:italic>CFTR<\/jats:italic>\n                    variant databases, with feedback incorporated from CF clinicians, genetic counselors, and CF content experts. Genotypes were determined to have very low, low, moderate, high, or very high likelihood of resulting in CF, CFTR\u2010related disorder (CFTR\u2010RD), no symptoms, or the designation of CFTR\u2010related metabolic syndrome\/CF\u2010screen positive, inconclusive diagnosis (CRMS\/CFSPID) following CF newborn screening. The resource described in this report is intended to help clinicians navigate the uncertainty surrounding potential diagnostic scenarios to present accurate assessments to patients and families, a critical component of CF genetic testing and counseling.\n                  <\/jats:p>","DOI":"10.1002\/jgc4.70151","type":"journal-article","created":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T18:42:13Z","timestamp":1766947333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Developing a primer for communicating about penetrance, expressivity, and genotype\u2013phenotype correlation of\n                    <scp>R117H<\/scp>\n                    and the poly\u2010T tract in\n                    <i>CFTR<\/i>"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-6854","authenticated-orcid":false,"given":"Karen S.","family":"Raraigh","sequence":"first","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-480X","authenticated-orcid":false,"given":"Jessica R.","family":"Balcom","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Laboratory Medicine and Pathology, Department of Pediatric and Adolescent Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8119-7559","authenticated-orcid":false,"given":"Elinor","family":"Langfelder\u2010Schwind","sequence":"additional","affiliation":[{"name":"Department of Pulmonary, Critical Care, and Sleep Medicine Lenox Hill Hospital, Northwell Health  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,28]]},"reference":[{"issue":"4","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jcf.2019.07.001","article-title":"Nasal potential difference in suspected cystic fibrosis patients with 5T polymorphism","volume":"19","author":"Aalbers B. 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N.","year":"2011","journal-title":"Rhinology"},{"issue":"2","key":"e_1_2_15_12_1","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00431-023-05359-5","article-title":"Risk of CFTR\u2010related disorders and cystic fibrosis in an Italian cohort of CRMS\/CFSPID subjects in preschool and school age","volume":"183","author":"Fevola C.","year":"2024","journal-title":"European Journal of Pediatrics"},{"key":"e_1_2_15_13_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/(SICI)1098-1004(1997)10:2<108::AID-HUMU3>3.0.CO;2-G","article-title":"Rapid characterization of the variable length polythymidine tract in the cystic fibrosis (CFTR) gene: Association of the 5T Allel with selected CFTR mutations and its incidence in atypical sinopulmonary disease","volume":"10","author":"Friedman K.","year":"1997","journal-title":"Human Mutation"},{"issue":"6","key":"e_1_2_15_14_1","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2021-051740","article-title":"Outcomes of cystic fibrosis screening\u2010positive infants with inconclusive diagnosis at school age","volume":"148","author":"Gonska T.","year":"2021","journal-title":"Pediatrics"},{"issue":"1","key":"e_1_2_15_15_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1086\/381001","article-title":"Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign","volume":"74","author":"Groman J. 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L.","year":"2017","journal-title":"The Journal of Pediatrics"},{"issue":"12","key":"e_1_2_15_26_1","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1002\/ppul.27184","article-title":"Literary evidence of the impact of nonbiological risk factors on CRMS\/CFSPID: A scoping review","volume":"59","author":"Rose N. R.","year":"2024","journal-title":"Pediatric Pulmonology"},{"issue":"3","key":"e_1_2_15_27_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s41030-025-00303-4","article-title":"Impact of CFTR modulators on longitudinal cystic fibrosis survival and mortality: Review and secondary analysis","volume":"11","author":"Rubin J. 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B.","year":"2016","journal-title":"PLoS One"},{"issue":"6","key":"e_1_2_15_31_1","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.jcf.2012.12.014","article-title":"Impaired CFTR function in mild cystic fibrosis associated with the S977F\/T5TG12complex allele in trans with F508del mutation","volume":"12","author":"Sorio C.","year":"2013","journal-title":"Journal of Cystic Fibrosis"},{"issue":"10","key":"e_1_2_15_32_1","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/ng.2745","article-title":"Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene","volume":"45","author":"Sosnay P. R.","year":"2013","journal-title":"Nature Genetics"},{"issue":"11","key":"e_1_2_15_33_1","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1136\/jmg.2009.067215","article-title":"The very low penetrance of cystic fibrosis for the R117H mutation: A reappraisal for genetic counselling and newborn screening","volume":"46","author":"Thauvin\u2010Robinet C.","year":"2009","journal-title":"Journal of Medical Genetics"},{"issue":"4","key":"e_1_2_15_34_1","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1002\/ppul.26323","article-title":"Clinical outcome of individuals carrying 5T;TG12 in trans with CFTR variants with varying clinical consequences","volume":"58","author":"Tosco A.","year":"2023","journal-title":"Pediatric Pulmonology"},{"issue":"5","key":"e_1_2_15_35_1","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jcf.2022.04.020","article-title":"Clinical outcomes of a large cohort of individuals with the F508del\/5T;TG12 CFTR genotype","volume":"21","author":"Tosco A.","year":"2022","journal-title":"Journal of Cystic Fibrosis"}],"container-title":["Journal of Genetic Counseling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgc4.70151","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T18:42:18Z","timestamp":1766947338000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgc4.70151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jgc4.70151"],"URL":"https:\/\/doi.org\/10.1002\/jgc4.70151","archive":["Portico"],"relation":{},"ISSN":["1059-7700","1573-3599"],"issn-type":[{"value":"1059-7700","type":"print"},{"value":"1573-3599","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70151"}}