ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.5014_5015del (p.Arg1672fs) (rs1555455457)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518367 SCV000614505 pathogenic not provided 2015-12-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000518367 SCV000884357 pathogenic not provided 2017-11-28 criteria provided, single submitter clinical testing The PKD1 c.5014_5015delAG, p.Arg1672fs variant is a recurrent alteration in patients diagnosed with autosomal dominant polycystic kidney disease (Audrezet 2012, Garcia-Gonzalez 2007, Hoefele 2011, Mallawaarachchi 2016, Rossetti 2003, Rossetti 2007, Rossetti 2012, Thongnoppakhun 2004, Watnick 1999). It is listed as definitely pathogenic in the Mayo ADPKD database (see link), and not observed in the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database). The variant introduces a frameshift, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the p.Arg1672fs variant is classified as pathogenic. References: Audrezet M et al. Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum Mutat. 2012; 33(8):1239-50. Garcia-Gonzalez M et al. Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. Mol Genet Metab. 2007; 92(1-2):160-7. Hoefele J et al. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2011; 26(7):2181-8. Mallawaarachchi A et al. Whole-genome sequencing overcomes pseudogene homology to diagnose autosomal dominant polycystic kidney disease. Eur J Hum Genet. 2016; 24(11):1584-1590. Rossetti S et al. Association of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype. Lancet. 2003; 361(9376):2196-201. Rossetti S et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007; 18(7):2143-60. Rossetti S et al. Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing. J Am Soc Nephrol. 2012; 23(5):915-33. Thongnoppakhun W et al. Novel and de novo PKD1 mutations identified by multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP). BMC Med Genet. 2004; 5:2. Watnick T et al. Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease. Am J Hum Genet. 1999; 65(6):1561-71.
Mendelics RCV000989457 SCV001139787 pathogenic Polycystic kidney disease, adult type 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000518367 SCV001167826 pathogenic not provided 2018-09-12 criteria provided, single submitter clinical testing The c.5014_5015delAG variant has been published previously in association with polycystic kidney disease (Watnick et al., 1999; Carrera et al., 2016; Iliuta et al., 2017). The variant is not observed in large population cohorts (Lek et al., 2016). The deletion causes a frameshift starting with codon Arginine 1672, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 98 of the new reading frame, denoted p.Arg1672GlyfsX98. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Cavalleri Lab, Royal College of Surgeons in Ireland RCV000989457 SCV001251206 pathogenic Polycystic kidney disease, adult type 2020-02-05 criteria provided, single submitter research PVS1, PM2, PP4
Gharavi Laboratory,Columbia University RCV000518367 SCV000809134 pathogenic not provided 2018-09-16 no assertion criteria provided research
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000989457 SCV001192668 pathogenic Polycystic kidney disease, adult type 2019-11-27 no assertion criteria provided clinical testing

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