ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.2180T>C (p.Leu727Pro) (rs1616940)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000681747 SCV000843112 likely pathogenic not provided 2019-05-09 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/154898 chr). Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000681747 SCV000884348 likely pathogenic not provided 2018-01-21 criteria provided, single submitter clinical testing The PKD1 c.2180T>C; p.Leu727Pro variant (rs1616940) is reported in the literature in 27 unrelated patients with autosomal dominant polycystic kidney disease (Audrezet 2012, Carrera 2016, Cornec-Le Gall 2013, Hoefele 2011, Rossetti 2007, Rosetti 2012, Tan 2014) and is also listed on gene-specific databases (Mayo ADPKD Mutation Database) . This variant is absent from the general population with an average of 126647 alleles reported for this genomic region (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The leucine at codon 727 is highly conserved and computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be damaging. Based on the above information, this variant is considered likely pathogenic. References: Mayo ADPKD Mutation Database: Audrezet M 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. Carrera P et al. Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Sci Rep. 2016; 6: 30850. Cornec-Le Gall E et al. Type of PKD1 mutation influences renal outcome in ADPKD. J Am Soc Nephrol. 2013 May;24(6):1006-13. Hoefele J et al. Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2011 Jul;26(7):2181-8. Rossetti S et al. Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2007 Jul;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 May;23(5):915-33. Tan A et al. Molecular diagnosis of autosomal dominant polycystic kidney disease using next-generation sequencing. J Mol Diagn. 2014 Mar;16(2):216-28.
Molecular Diagnostics Laboratory, M Health: University of Minnesota RCV000761328 SCV000891313 likely pathogenic Polycystic kidney disease 3 2018-03-28 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000681747 SCV000928102 pathogenic not provided 2018-12-05 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000681747 SCV000809204 pathogenic not provided 2018-09-16 no assertion criteria provided research

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