ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.3383T>C (p.Ile1128Thr)

gnomAD frequency: 0.00001  dbSNP: rs78624439
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
Labcorp Genetics (formerly Invitae), Labcorp RCV002000742 SCV002270790 likely pathogenic Autosomal recessive polycystic kidney disease 2024-05-08 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1128 of the PKHD1 protein (p.Ile1128Thr). This variant is present in population databases (rs78624439, gnomAD 0.006%). This missense change has been observed in individual(s) with PKHD1-related conditions (PMID: 24162162). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1482161). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV003234151 SCV003930505 uncertain significance not provided 2022-12-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24162162)
Baylor Genetics RCV003475268 SCV004202249 likely pathogenic Polycystic kidney disease 4 2024-03-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV003475268 SCV005671426 uncertain significance Polycystic kidney disease 4 2024-06-17 criteria provided, single submitter 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.