Submissions for variant NM_001009944.3(PKD1):c.11379del (p.Thr3794fs)

dbSNP: rs1567153758

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001312	SCV001158494	pathogenic	Polycystic kidney disease, adult type	2019-05-16	criteria provided, single submitter	clinical testing	The PKD1 c.11379delG; p.Thr3794fs variant, also called c.11587delG using alternative nomenclature, is reported in the literature in multiple individuals affected with autosomal dominant polycystic kidney disease (Audrezet 2012, Bogdanova 2000, Garcia-Gonzalez 2007, Rossetti 2012) and has been reported to segregate with disease in at least one family (Bogdanova 2000). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Audrezet MP et al. Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum Mutat. 2012 Aug;33(8):1239-50. Bogdanova N et al. Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene in 41 Bulgarian and Australian kindreds reveals a prevalence of protein truncating mutations. Hum Mutat. 2000;16(2):166-74. Garcia-Gonzalez MA et al. Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. Mol Genet Metab. 2007 Sep-Oct;92(1-2):160-7. Rossetti S et al. Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing. J Am Soc Nephrol. 2012 May;23(5):915-33.
GeneDx	RCV000681729	SCV001982785	pathogenic	not provided	2025-03-20	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22508176, 17574468, 31874800, 10923038, 38527221, 22383692, 30586318)
PreventionGenetics, part of Exact Sciences	RCV003424276	SCV004117887	pathogenic	PKD1-related disorder	2023-08-07	criteria provided, single submitter	clinical testing	The PKD1 c.11379delG variant is predicted to result in a frameshift and premature protein termination (p.Thr3794Argfs*32). This variant has been reported to be pathogenic for autosomal dominant polycystic kidney disease (Bogdanova et al. 2000. PubMed ID: 10923038; Table S7, Groopman et al. 2018. PubMed ID: 30586318; Hopp et al. 2019. PubMed ID: 31874800). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in PKD1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001001312	SCV005184203	pathogenic	Polycystic kidney disease, adult type	2024-07-19	criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS4_Supporting+PP4
Fulgent Genetics, Fulgent Genetics	RCV001001312	SCV005638797	pathogenic	Polycystic kidney disease, adult type	2024-05-06	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005357906	SCV005913930	pathogenic	Autosomal dominant polycystic kidney disease	2021-03-12	criteria provided, single submitter	clinical testing
Gharavi Laboratory, Columbia University	RCV000681729	SCV000809184	pathogenic	not provided	2018-09-16	no assertion criteria provided	research