ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.23T>C (p.Leu8Pro)

gnomAD frequency: 0.00001  dbSNP: rs750588859
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633432 SCV000754656 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 8 of the PKHD1 protein (p.Leu8Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs750588859, ExAC 0.001%). This missense change has been observed in individual(s) with polycystic kidney disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001569911 SCV001794080 uncertain significance not provided 2021-05-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV003432661 SCV004117702 likely pathogenic PKHD1-related condition 2023-12-01 criteria provided, single submitter clinical testing The PKHD1 c.23T>C variant is predicted to result in the amino acid substitution p.Leu8Pro. With a frameshifting variant, this variant has been reported in an individual with autosomal recessive polycystic kidney disease (ARPKD) (Burgmaier et al. 2021. PubMed ID: 33940108, Supplementary Table). In addition, at PreventionGenetics, we also found this variant in the compound heterozygous state with another frameshift variant in a patient tested for ARPKD. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic.
Natera, Inc. RCV000633432 SCV001453293 uncertain significance Autosomal recessive polycystic kidney disease 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.