ClinVar

Description

Variant summary: CFTR c.1678A>G (p.Arg560Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: One predicts the variant abolishes a 5' splicing donor site and one predicts the variant weakens a 5' donor site. Two predict the variant has no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250518 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1678A>G has been reported in the literature in individuals affected with Cystic Fibrosis (e.g. Alonso_2007, Moya-Quiles_2009, de Dios Caballero_2016), including one compound heterozygote with a known second pathogenic allele (Sickkids database). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.