ClinVar

Description

Variant summary: CFTR c.3038C>T (p.Pro1013Leu) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251138 control chromosomes. c.3038C>T has been reported in the literature in the compound heterozygous state or an unknown state in multiple individuals affected with clinical features of Cystic Fibrosis and/or testing positive for CF upon NBS (example, Onay_1998, Kilinc_2002, Elahi_2006, Narzi_2007, Schippa_2013, Lucarelli_2015, Castaldo_2020, Bozdogan_2021, Erdoan_2021, Saferali_2022), including at least 1 family where 2 siblings carried a pathogenic variant in trans segregating with disease. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect resulted in approximately 30.71% of normal chloride channel conductance relative to wild type (e.g., Bihler_2024). The following publications have been ascertained in the context of this evaluation (PMID: 12007216, 33572515, 32784480, 11504857, 16436643, 34860163, 11278813, 34426522, 12439892, 25880441, 25910067, 17594398, 9521595, 25735457, 34996830, 23613805, 26437683, 38388235). ClinVar contains an entry for this variant (Variation ID: 53634). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.