ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.9829C>T (p.Arg3277Cys) (rs148812376)

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
GeneDx RCV000497386 SCV000589517 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing The R3277C variant in the PKD1 gene has been reported previously in the heterozygous, homozygous, and compound heterozygous state associated with variable severity of polycystic kidney disease (Rossetti et al., 2009; Audrézet et al., 2016). The R3277C variant was identified through four generations of a consanguineous family; two siblings homozygous for the R3277C variant developed end stage renal disease at age 62 and 75 whereas 6 additional heterozygous family members had few renal cysts (Rossetti et al., 2009). The R3277C variant has also been seen in trans with another disease causing variant in association with in utero polycystic kidney disease (Rossetti et al., 2009; Audrézet et al., 2016). In addition, a knockin mouse model demonstrated mice that were heterozygous for the 3277C variant had no clinical features, homozygous mice developed gradual cystogenesis, and mice that were compound heterozygous for the 3277C variant and the null allele had rapidly progressive disease (Hopp et al., 2012). The R3277C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R3277Cvariant is a non-conservative amino acid substitution, which occurs at a position that is conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R3277C as a pathogenic variant.
GeneReviews RCV000192215 SCV000223894 pathogenic Polycystic kidney disease, adult type 2015-06-11 no assertion criteria provided literature only
Gharavi Laboratory,Columbia University RCV000497386 SCV000920751 likely benign not provided 2018-09-16 no assertion criteria provided research

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.