ClinVar

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1290 of the CFTR protein (p.Pro1290Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with congenital bilateral absence of the vas deferens (PMID: 15705389). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 4000C>T. ClinVar contains an entry for this variant (Variation ID: 53825). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function. Experimental studies have shown that this missense change affects CFTR function (PMID: 18769034). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.