ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.9561CAA[1] (p.Asn3188del) (rs869312944)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210674 SCV000262953 pathogenic Inborn genetic diseases 2013-08-07 criteria provided, single submitter clinical testing The c.9564_9566delCAA (p.N3188del) alteration is located in coding exon 27 of the PKD1gene. This alteration results from an in-frame deletion from nucleotide position 9564 through 9566, resulting in the deletion of asperagine at codon 3188. The alteration is not observed in healthy cohorts:Based on data from the NHLBI Exome Sequencing Project (ESP), the PKD1 c.9564_9566delCAA (p.N3188del) alteration was not observed among 6,498 individuals tested (0.0%). Allele frequency data for this nucleotide position is not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP). The altered amino acid is conserved throughout evolution:The p.N3188 amino acid is conserved throughout vertebrates. The amino acid is located in a functionally important protein domain:The c.9564_9566delCAA (p.N3188del) alteration is located within the fhe first cytoplasmic loop in the transmembrane region of the PKD1 gene, a region which is among the highest regions of conservation in the gene (Stanford et al., 1997).The amino acid change has been observed in affected individuals:This alteration has been described in the literature (see below for details) and is observed in the HGMD database (CD034171). The alteration was identifed in a female proband with ADPKD renal findings in addition to a vascular phenotype which was described as a ruptured intracranial aneurysm at the age of 31 (Rosetti et al., 2003).The alteration has cosegregated with disease:This PKD1 alteration was detected in our laboratory via exome sequencing in a patient with ADPKD (12-64954). The alteration co-segregated with the disease, as the affected father (12-64956) also manifested the alteration.Based on the available evidence, the PKD1 c.9564_9566delCAA (p.N3188del) alteration is classified as a pathogenic mutation.Rosetti S, et al. (2003) Lancet 361:2196-2201.Stanford R, et al. (1997) Hum Mol Genet 6(9):1483–1489.
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV001254254 SCV001430294 likely pathogenic Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research

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