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In CFTR-RD, <jats:italic>CFTR<\/jats:italic> genotyping represents a diagnostic surrogate marker. In case of novel haplotype, the diagnosis could represents an area of concern. We described the molecular evaluation of the rare <jats:italic>CFTR<\/jats:italic> variant E583G identified <jats:italic>in trans<\/jats:italic> with the F508del in a novel haplotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and results<\/jats:title>\n            <jats:p>An adult woman was referred to our pulmonary unit for persistent respiratory symptoms. <jats:italic>CFTR<\/jats:italic> Next Generation Sequencing was performed to evaluate full-gene mutational status. The variant identified was evaluated for its pathogenicity integrating clinical evidences with dedicated bioinformatics analyses. Clinical evaluation of patient matched with a mono-organ CFTR-RD diagnosis. Genotyping revealed the novel <jats:italic>CFTR<\/jats:italic> haplotype F508del\/E583G. Multiple evidences of a deleterious effect of the <jats:italic>CFTR<\/jats:italic> E583G rare variant emerged from the bioinformatics analyses performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Guidelines for CFTR-RD are available with the purpose of harmonizing clinical and molecular investigations. In such context, the identification of novel <jats:italic>CFTR<\/jats:italic> haplotype need to a deeper evaluation with a combination of skills. The novel E583G variant could be considered of clinical interest and overall a CFTR-RD Variants of Varying Clinical Consequences.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11033-024-09732-x","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T08:01:54Z","timestamp":1721894514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The novel CFTR haplotype E583G\/F508del in CFTR-related disorder"],"prefix":"10.1007","volume":"51","author":[{"given":"Elisa","family":"De Paolis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Tilocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Inchingolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Perrucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Maneri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Roncada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Varone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richeldi","family":"Luca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Minucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Santonocito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"9732_CR1","first-page":"1341","volume":"12","author":"CA Schram","year":"2012","unstructured":"Schram CA (2012) Atypical cystic fibrosis: identification in the primary care setting. 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