ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.10939C>T (p.Arg3647Trp)

gnomAD frequency: 0.00024  dbSNP: rs181927900
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
Athena Diagnostics RCV000712578 SCV000843094 uncertain significance not provided 2018-08-03 criteria provided, single submitter clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research RCV000712578 SCV001422360 uncertain significance not provided 2019-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000712578 SCV002552688 uncertain significance not provided 2022-07-14 criteria provided, single submitter clinical testing Reported with a second PKD1 variant (phase unknown) in a patient with polycystic kidney disease in published literature (Mallawaarachchi et al., 2021); 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: 33437033)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005407917 SCV006073201 uncertain significance not specified 2025-04-03 criteria provided, single submitter clinical testing Variant summary: PKD1 c.10939C>T (p.Arg3647Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 240446 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in PKD1 causing PKD1-Biallelic Autosomal Recessive Polycystic Kidney Disease, allowing no conclusion about variant significance. c.10939C>T has been reported in the literature in individuals affected with Autosomal Dominant Polycystic Kidney Disease or connective tissue disorders (Mallawaarachchi_2021, Steinle_2022). These reports do not provide unequivocal conclusions about association of the variant with PKD1-Biallelic Autosomal Recessive Polycystic Kidney Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33437033, 35903967). ClinVar contains an entry for this variant (Variation ID: 586244). Based on the evidence outlined above, the variant was classified as uncertain 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.