Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756522 | SCV000884356 | likely pathogenic | not provided | 2017-12-07 | criteria provided, single submitter | clinical testing | The PKD1 c.12724C>T, p.Gln4242Ter variant has been reported in two individuals with autosomal dominant polycystic kidney disease (Hoefele 2010, Strekova 2009), and listed as definitely pathogenic in the Mayo ADPKD database (see link). It is not observed in the general population databases, such as the 1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database. The variant introduces a premature termination codon in the last exon, and is predicted to result in a truncated protein lacking 62 amino acids at the C-terminus. Nearby and downstream truncating variants have also been reported in individuals with autosomal dominant polycystic kidney disease (Mayo ADPKD database). Based on the above information, the p.Gln4242Ter variant is classified as likely pathogenic. References: Mayo ADPKD database: http://pkdb.mayo.edu/ Hoefele J et al. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2011; 26(7):2181-8. Stekrova J et al. New mutations in the PKD1 gene in Czech population with autosomal dominant polycystic kidney disease. BMC Med Genet. 2009; 10:78. |
| Gene |
RCV000756522 | SCV001813243 | likely pathogenic | not provided | 2021-01-06 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 62 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19686598, 21115670) |
| Fulgent Genetics, |
RCV002507324 | SCV002810527 | likely pathogenic | Polycystic kidney disease, adult type | 2021-09-24 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003396317 | SCV004104893 | likely pathogenic | PKD1-related condition | 2023-07-19 | criteria provided, single submitter | clinical testing | The PKD1 c.12724C>T variant is predicted to result in premature protein termination (p.Gln4242*). This variant has been reported in an individual with polycystic kidney disease 1 (Table 1, Stekrova et al. 2009. PubMed ID: 19686598). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in PKD1 are expected to be pathogenic. Of note, this variant resides in the final exon of this gene, and it is unclear if the resulting mRNA would undergo nonsense-mediated decay. This variant is interpreted as likely pathogenic. |