Submissions for variant NM_001009944.3(PKD1):c.11884C>T (p.Gln3962Ter)

dbSNP: rs1596476503

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002070118	SCV002496217	pathogenic	not provided	2022-12-08	criteria provided, single submitter	clinical testing	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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29529603, 24694054)
Fulgent Genetics, Fulgent Genetics	RCV002504424	SCV002811017	pathogenic	Polycystic kidney disease, adult type	2022-05-16	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292123	SCV001480980	pathogenic	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Gln3962* variant was identified in 3 of 322 proband chromosomes (frequency: 0.009) from individuals or families with ADPKD (Audrezet 2016 ,Xu 2018). The variant was also identified in LOVD 3.0 (1x as "affects function"), and the ADPKD Mutation Database (1x as definitely pathogenic by Athena Diagnostics). The variant was not identified in dbSNP, ClinVar, Clinvitae, COGR, or PKD1-LOVD databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.11884C>T variant leads to a premature stop codon at position 3962 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PKD1 gene are an established mechanism of disease in ADPKD and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.