Submissions for variant NM_001009944.3(PKD1):c.7204C>T (p.Arg2402Ter)

dbSNP: rs1567186946

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000712646	SCV000843164	pathogenic	not provided	2018-08-03	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000712646	SCV000927973	pathogenic	not provided	2018-10-04	criteria provided, single submitter	clinical testing
Molecular Biology Laboratory, Fundació Puigvert	RCV001281267	SCV001425192	pathogenic	Polycystic kidney disease, adult type	2020-02-01	criteria provided, single submitter	research
GeneDx	RCV000712646	SCV001872626	pathogenic	not provided	2022-06-21	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: 33532864, Izzi2020[abstract], 29529603, 11012875, 29633482, 22508176, 25333066, 25525159)
Fulgent Genetics, Fulgent Genetics	RCV001281267	SCV002790539	pathogenic	Polycystic kidney disease, adult type	2022-03-17	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292115	SCV001480947	pathogenic	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKD1 p.Arg2402* variant was identified in 7 of 3596 proband chromosomes (frequency: 0.002) from individuals or families with autosomal dominant polycystic kidney disease and was not identified in 110 control chromosomes from healthy individuals (Xu 2018, Neumann 2013, Trujillano 2014, Phakdeekitcharoen 2000, Audrézet 2012, Hwang 2016). It was also identified in ClinVar (1x as Pathogenic by one submitter) and in the ADPKD Mutation Database (classified as Definitely Pathogenic). The variant was not identified in dbSNP, LOVD 3.0 or in the PKD1-LOVD databases. It was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Arg2402* variant leads to a premature stop codon at position 2402, 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 autosomal dominant polycystic kidney disease 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.