ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2T>C (p.Met1Thr)

dbSNP: rs2128246846
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001377569 SCV001574937 pathogenic Autosomal recessive polycystic kidney disease 2021-04-20 criteria provided, single submitter clinical testing This variant disrupts the initiator methionine in PKHD1. If translation initiates from the next in-frame methionine, the PKHD1 protein would no longer include the region containing the p.Leu8 amino acid residue. Other variant(s) that disrupt this residue have been observed in individuals with PKHD1-related conditions (Invitae), which suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 27225849). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the PKHD1 mRNA. The next in-frame methionine is located at codon 9.

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.