ClinVar

Description

Variant summary: CFTR c.1163C>T (p.Thr388Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 250946 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CFTR causing CFTR-Related Diseases (0.00016 vs 0.013), allowing no conclusion about variant significance. c.1163C>T has been reported in the literature as heterozygous in individuals affected with CFTR-Related Diseases including CF, CBAVD/CUAVD, asthma, and in children with positive newborn screening, without strong evidence for causality (example, Schrijver_2016, Dayangac_2004, Akinsal_2018, Tzetis_2001, Bozdogan_2021). These reports do not provide unequivocal conclusions about association of the variant with CFTR-Related Diseases. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect resulted in approximately 86.1% 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: 26990548, 29484681, 33572515, 15070876, 29589582, 26708955, 11354633, 38388235). ClinVar contains an entry for this variant (Variation ID: 495887). Based on the evidence outlined above, the variant was classified as uncertain significance.