ClinVar

Description

Variant summary: CFTR c.1175T>C (p.Val392Ala) results in a non-conservative amino acid change located in the ATP-binding cassette domain (IPR047082) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250960 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1175T>C has been reported in the literature in at least one compound heterozygous individual affected with Congenital Bilateral Absence Of The Vas Deferens, in trans with the F508del variant (e.g., Chen_2001, Dorfman_2010, SickKids Cystic Fibrosis Mutation 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. The following publications have been ascertained in the context of this evaluation (PMID: 11504857, 20059485, 35913788). One ClinVar submitter (evaluation after 2014) has cited the variant and classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.