ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10973T>C (p.Ile3658Thr) (rs142536551)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460905 SCV000545852 uncertain significance Autosomal recessive polycystic kidney disease 2019-01-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3658 of the PKHD1 protein (p.Ile3658Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs142536551, ExAC 0.06%) but has not been reported in the literature in individuals with a PKHD1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733283 SCV000861329 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000460905 SCV001327048 uncertain significance Autosomal recessive polycystic kidney disease 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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.