Description
The PKD1 p.His728Arg variant was not identified in the literature nor was it identified in the ClinVar, LOVD 3.0, ADPKD Mutation Database, or PKD1-LOVD, databases. The variant was identified in dbSNP (ID: rs1050939771). The variant was also identified in our laboratory with co-occuring pathogenic PKD1 variant (c.2961_2977del (p.Ser988Alafs*107)), increasing the likelihood that the p.His728Arg variant does not have clinical significance. The variant was identified in control databases in 5 of 150234 chromosomes at a frequency of 0.000033 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 14832 chromosomes (freq: 0.000067), European in 2 61258 chromosomes (freq: 0.000033), and South Asian in 2 of 19184 chromosomes (freq: 0.0001), while the variant was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, and 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.His728 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |