rs2091385750

Description

The PKD1 p.Gly4261Ser variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, LOVD 3.0, ADPKD Mutation Database, PKD1-LOVD, Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant was identified in our laboratory in an individual with a pathogenic PKD1 variant (p.Glu1741x). The p.Gly4261 residue is conserved in in mammals but not in more distantly related organisms however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.