ClinVar

Description

The CFTR c.2939T>A; p.Ile980Lys variant (rs397508463) is reported in the literature in multiple individuals affected with congenital absence of the vas deferens (CBAVD) or cystic fibrosis (CF) (Bienvenu 1996, Hubert 1996, Jezequel 2000, Steiner 2011). In all affected individuals carrying this variant, a second pathogenic variant was also identified (Bienvenu 1996, Hubert 1996, Jezequel 2000, Steiner 2011). The p.Ile980Lys variant is present on only two chromosomes (2/251150 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. The isoleucine at codon 980 is moderately conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Despite its prevalence in affected individuals, due to limited information, the significance of the p.Ile980Lys variant is uncertain at this time. References: Bienvenu T et al. A novel missense mutation in exon 16 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene identified in CBAVD patients. Hum Mutat. 1996;7(2):182. Hubert D et al. Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients. Eur Respir J. 1996 Nov;9(11):2207-14. Jezequel P et al. Molecular screening of the CFTR gene in men with anomalies of the vas deferens: identification of three novel mutations. Mol Hum Reprod. 2000 Dec;6(12):1063-7. Steiner B et al. Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. Hum Mutat. 2011 Aug;32(8):912-20.