ClinVar

Description

Variant summary: CFTR c.1369G>C (p.Ala457Pro) results in a non-conservative amino acid change located in the P-loop containing nucleoside triphosphate hydrolase domain (IPR027417) of the encoded protein. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 270602 control chromosomes (in gnomAD), thus the available data on the variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1369G>C has been reported in the literature in one individual, in compound heterozygous state with the F508del, who was presenting with milder CF-related symptoms (i.e. recurrent bouts of bronchitis and probable CABDV, without pancreatic insufficiency; Cole 2011), however more data is required to 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 VUS.