rs2091397048

Description

The PKD1 p.Glu4220* variant was identified in 1 of 404 proband chromosomes (frequency: 0.003) from individuals or families with autosomal dominant polycystic kidney disease (Rossetti 2007). The variant was also identified in ADPKD Mutation Database (as definitely pathogenic). The variant was not identified in the dbSNP, ClinVar, LOVD 3.0, or PKD1-LOVD databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). One study reports that the p.Glu4220* variant occurs within the PKD1 coiled-coil domain, the site of PKD2 binding (Gainullin, 2015). The p.Glu4220* variant leads to a premature stop codon at position 4220, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PKD1 gene are an established mechanism of disease in autosomal dominant polycystic kidney disease and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.