Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001292140 | SCV001480665 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Val690Ile variant was identified in 1 of 296 proband chromosomes (frequency: 0.003) from Chinese individuals or families with ADPKD (Jin_2016). The variant was also identified in dbSNP (ID: rs948344824), and in control databases in 1 of 165228 chromosomes at a frequency of 0.000006 (Genome Aggregation Database Feb 27, 2017). It was observed in the South Asian population in 1 of 24174 chromosomes (freq: 0.00004), but not in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, East Asian and Finnish populations. The variant was not identified in ClinVar, COGR, LOVD 3.0, ADPKD Mutation Database, and PKD1-LOVD databases. The p.Val690 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact of the variant Ile 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, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified in our laboratory in 1 individual with ADPKD, co-occurring with a pathogenic PKD1 variant (c.2494dupC, p.Arg832ProfsX40), increasing the likelihood it does not have clinical significance. 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. |