ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.12010C>T (p.Gln4004Ter) (rs766551411)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504063 SCV000592859 pathogenic Autosomal recessive polycystic kidney disease 2016-10-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000681726 SCV000885951 pathogenic not provided 2017-08-31 criteria provided, single submitter clinical testing The PKD1 c.12010C>T; p.Gln4004Ter variant (rs766551411) has been reported in two families with autosomal dominant polycystic kidney disease, and segregating with affected individuals (Audrezet 2012). An immortalized cell line carrying the variant shows reduced PKD1 incorporation in the cellular membrane, and absence in the primary cilia (Herbert 2013). This variant is reported as pathogenic in ClinVar (Variation ID: 434006), and is observed in the general population at a low overall frequency of 0.0004% (1/240348 alleles) in the Genome Aggregation Database. This variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the 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. Herbert B et al. A telomerase immortalized human proximal tubule cell line with a truncation mutation (Q4004X) in polycystin-1. PLoS One. 2013; 8(1):e55191.
Blueprint Genetics RCV000681726 SCV000927280 pathogenic not provided 2017-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000681726 SCV001167685 pathogenic not provided 2019-08-06 criteria provided, single submitter clinical testing Identified in patients with autosomal dominant polycystic kidney disease in published literature (Andrezet et al., 2012; Tujillano et al., 2014; Lorenzo-Betancor et al., 2018); Nonsense 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 at a significant frequency in large population cohorts (Lek et al., 2016)
Gharavi Laboratory,Columbia University RCV000681726 SCV000809179 pathogenic not provided 2018-09-16 no assertion criteria provided research

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