ClinVar

Description

The p.Arg1070Trp variant in CFTR has been reported in >20 compound heterozygous individuals (the majority carrying p.Phe508del) primarily affected by milder for ms of CFTR-related disorders (congenital bilateral absence of the vas deferens a nd cystic fibrosis) and more than half of these individuals were reported to hav e normal to low sweat chloride levels (Jezequel 1995, Feldmann 2003, Krasnov 200 8, Pelletier 2010, de Prada Merino 2010, Steiner 2011, Sosnay 2013). In addition , this variant has been identified in 4/66100 of European chromosomes and 1/1034 0 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs202179988). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessiv e carrier frequency. In vitro functional studies provide some evidence that the p.Arg1070Trp variant may impact protein function (Krasnov 2008, Sosnay 2013, Van Goor 2014). However, these types of assays may not accurately represent biologi cal function. In summary, this variant meets our criteria to be classified as pa thogenic for CTFR-related disorders including CBAVD and cystic fibrosis in an au tosomal recessive manner (http://www.partners.org/personalizedmedicine/LMM) base d upon multiple co-occurrences with pathogenic variants and its low frequency in the general population.