ClinVar

Description

Variant summary: CFTR c.1675G>C (p.Ala559Pro) results in a non-conservative amino acid change located in the ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250586 control chromosomes (gnomAD). c.1675G>C has been reported in the literature in the homozygous state in an individual affected with Cystic Fibrosis who was identified through a newborn screening program (Ibarra-Gonzalez_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, another variant affecting the same amino acid (c.1675G>A, p.Ala559Thr) has been classified as pathogenic, suggesting Ala559 may be important for protein function. The following publication have been ascertained in the context of this evaluation (PMID: 28992757). No submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.