Submissions for variant NM_001009944.3(PKD1):c.6736C>T (p.Gln2246Ter)

dbSNP: rs1567191534

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756531	SCV000884366	pathogenic	not provided	2018-06-21	criteria provided, single submitter	clinical testing	The PKD1 c.6736C>T; p.Gln2246Ter variant has been described in individuals with autosomal dominant polycystic kidney disease (ADPKD; see link to Mayo ADPKD database, Trujillano 2014). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, truncating nonsense and frameshift variants in PKD1 are a common mechanism of disease, and several truncating variants downstream from codon 2246 have been described in individuals with ADPKD (Rossetti 2007, Trujillano 2014). Based on available information, this variant is considered pathogenic. References: Link to Mayo ADPKD database: http://pkdb.mayo.edu/cgi-bin/v2_display_mutations.cgi?GENE=PKD1&apkd_mode=PROD Rossetti S et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007 Jul;18(7):2143-60. Trujillano D et al. Diagnosis of autosomal dominant polycystic kidney disease using efficient PKD1 and PKD2 targeted next-generation sequencing. Mol Genet Genomic Med. 2014 Sep;2(5):412-21.
Fulgent Genetics, Fulgent Genetics	RCV001029873	SCV002787302	pathogenic	Polycystic kidney disease, adult type	2024-02-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003413545	SCV004108305	pathogenic	PKD1-related disorder	2023-06-12	criteria provided, single submitter	clinical testing	The PKD1 c.6736C>T variant is predicted to result in premature protein termination (p.Gln2246*). This variant was reported in a patient with autosomal dominant polycystic kidney disease (Trujillano et al 2014. PubMed ID: 25333066) and found in a family with polycystic liver disease (reported as CT variant, see Figure 6, Jin et al 2015. PubMed ID: 25741140). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant falls within a highly paralogous region. Allele frequency data should be interpreted with caution. Nonsense variants in PKD1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001029873	SCV005184293	pathogenic	Polycystic kidney disease, adult type	2024-07-19	criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS4_Supporting+PP4
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	RCV001029873	SCV001192662	pathogenic	Polycystic kidney disease, adult type	2019-11-26	no assertion criteria provided	clinical testing