rs201035636

Description

PKD1, EXON46, c.12473T>C, p.Met4158Thr, Heterozygous, Uncertain SignificancernThe PKD1 p.Met4158Thr variant was not identified in the literature nor was it identified in the following databases: ClinVar, LOVD 3.0, or PKD1-LOVD. The variant was identified in dbSNP (ID: rs201035636), and ADPKD Mutation Database (as Indeterminate). The variant was identified in control databases in 30 of 232604 chromosomes at a frequency of 0.0001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 8 of 32802 chromosomes (freq: 0.0002), European in 12 of 104488 chromosomes (freq: 0.0001), Ashkenazi Jewish in 10 of 8782 chromosomes (freq: 0.001); it was not observed in the African, Other, East Asian, Finnish, and South Asian populations. The p.Met4158 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume 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. Assessment Date: 2019/06/26.