rs751776839

Description

The PKD1 p.Thr4030Ile variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0, ADPKD Mutation Database, or PKD1-LOVD databases. It was identified in dbSNP (ID: rs751776839) as "NA". The variant was also identified in control databases in 18 of 273928 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 23752 chromosomes (freq: 0.00008), Latino in 2 of 34354 chromosomes (freq: 0.00006), European in 10 of 124220 chromosomes (freq: 0.00008), East Asian in 3 of 18808 chromosomes (freq: 0.0002), and South Asian in 1 of 30740 chromosomes (freq: 0.00003), while not observed in the Other, Ashkenazi Jewish or Finnish populations. In addition, we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.Thr4030 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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.