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We conducted a meta-analysis of CRMS\/CFSPID cases from manuscripts to describe how the diagnoses would change using two different variant panels: (1) only CF-causing CFTR variants (PanelCF-causing) and (2) CF-causing variants and VVCCs (PanelCF-causing+VVCCs). Using the PanelCF-causing, 8.7% had two CF-causing variants (reclassified as CF), while 91.3% had less than two CF-causing variants (reclassified as Undetected). Using the PanelCF-causing+VVCCs, 51.4% had either two VVCCs or one VVCC with one CF-causing variant detected (reclassified as CRMS\/CFSPD), 39.9% had less than two CF-causing variants detected (reclassified as Undetected), and 8.7% had two CF-causing variants (reclassified as CF). In conclusion, using the updated CFTR2 classification of CFTR variants significantly decreases the number of children with CRMS\/CFSPID and gives a definitive diagnosis of CF to some children while not detecting as many children who are unlikely to develop CF.<\/jats:p>","DOI":"10.3390\/ijns11030060","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:09:27Z","timestamp":1753891767000},"page":"60","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Refining CFTR-Related Metabolic Syndrome (CRMS)\/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) Diagnosis: Impact of CFTR2 Variant Classifications"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9476-0788","authenticated-orcid":false,"given":"MacKenzie","family":"Wyatt","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98105, USA"},{"name":"Center for Respiratory Biology and Therapeutics, Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98105, USA"},{"name":"Center for Respiratory Biology and Therapeutics, Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincoln","family":"Shade","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Informatics, Multidisciplinary Science, University of Kentucky, 725 Rose St Building, Suite 230, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"McGarry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98105, USA"},{"name":"Center for Respiratory Biology and Therapeutics, Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1001\/jama.2023.8120","article-title":"Cystic Fibrosis: A Review","volume":"329","author":"Ong","year":"2023","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"McGarry, M.E., Raraigh, K.S., Farrell, P., Shropshire, F., Padding, K., White, C., Dorley, M.C., Hicks, S., Ren, C.L., and Tullis, K. 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