CFTR Variant Frequencies and Newborn Screening Panel Performance in the Diverse CF Population Receiving Care in the State of Georgia

Cystic fibrosis (CF) newborn screening (NBS) aims to improve outcomes through early diagnosis, yet disparities in time to diagnosis remain. This study examines <i>CFTR</i> allele frequencies and variant panel performance among a diverse CF population in Georgia to inform recommendations for updating the NBS algorithm and improving equity. This cross-sectional study includes 969 people with CF (PwCF) from Georgia's accredited CF centers. <i>CFTR</i> variant frequencies were calculated according to race and ethnicity. Panel performance was evaluated for Georgia's current Luminex-39 variant test and three expanded panels. Statistical analyses compared detection rates across panels and demographic groups. Georgia's diverse CF population demonstrates a unique <i>CFTR</i> allelic variability compared to national data. Increasing panel size enhances case identification. A panel including 719 CF-causing variants from the CFTR2 database significantly improves case detection from 93% to 97% (<i>p</i> = 0.002), as well as two-variant detection from 69% to 86% (<i>p</i> < 0.001). Detection of minoritized PwCF also improves with increasing panel size. However, even using the 719-variant panel, detection of non-Hispanic Black PwCF remains significantly lower compared to non-Hispanic White PwCF (case detection: <i>p</i> = 0.003; two-variant detection: <i>p</i> < 0.001). In conclusion, the use of expanded <i>CFTR</i> panels for NBS in Georgia would enhance timely diagnosis and improve equity.