ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.11314C>T (p.Arg3772Ter)

gnomAD frequency: 0.00001  dbSNP: rs199839578
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411765 SCV000485553 likely pathogenic Autosomal recessive polycystic kidney disease 2016-01-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000411765 SCV000699844 pathogenic Autosomal recessive polycystic kidney disease 2017-05-29 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.11314C>T (p.Arg3772X) variant results in a premature termination codon, predicted to cause a truncated or absent PKHD1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic in ClinVar (e.g. p.Arg3842Ter and c.11776delG (p.Val3926Trpfs)). This variant is absent in 121176 control chromosomes from ExAC. This variant has been reported in five patients from four ARPKD families (Bergmann_2004, Melchionda_2016; Li_2016), in homozygous state and in compound heterozygous state with known, c.9689delA (p.Asp3230fs) and presumably pathogenic, c.889T>A (p.Cys297Ser) variants. Parents were genotyped in both families and variant transmission in affected offspring's was consistent with disease inheritance. One clinical diagnostic laboratory has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000411765 SCV000956252 pathogenic Autosomal recessive polycystic kidney disease 2023-11-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3772*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is present in population databases (rs199839578, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with polycystic kidney disease (PMID: 15108281, 27225849, 27577217). ClinVar contains an entry for this variant (Variation ID: 370289). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002504202 SCV002815484 pathogenic Polycystic kidney disease 4 2021-08-27 criteria provided, single submitter clinical testing
Baylor Genetics RCV002504202 SCV004202242 pathogenic Polycystic kidney disease 4 2023-10-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV000411765 SCV002075487 pathogenic Autosomal recessive polycystic kidney disease 2017-08-09 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.