ClinVar

Description

Variant summary: CFTR c.1736A>C (p.Asp579Ala) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250214 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1736A>C in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported in the literature, although the CFTR Locus-specific database reports a patient who had the variant in trans with a pathogenic variant. Another missense change affecting this amino acid has been determined to be pathogenic, suggesting this is a functionally important residue. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.