ClinVar

Description

Variant summary: CFTR c.3877G>A (p.Val1293Ile) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 2.8e-05 in 250000 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3877G>A has been reported in the literature in at least one individual affected with Cystic Fibrosis (e.g., El-Seedy_2016), however without strong evidence for causality. This report therefore does not provide unequivocal conclusions about association of the variant with Cystic Fibrosis. At least one publication reports experimental evidence evaluating an impact on protein function (e.g., Bihler_2023, no PMID). These results showed no damaging effect of this variant. The following publications have been ascertained in the context of this evaluation (PMID: 28040058, 11379874, 20974851, 15536480, 16251901, 17244607). ClinVar contains an entry for this variant (Variation ID: 552594). Based on the evidence outlined above, the variant was classified as uncertain significance.