Submissions for variant NM_001009944.3(PKD1):c.2085dup (p.Ala696fs)

dbSNP: rs1567212531

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000681754	SCV000928155	pathogenic	not provided	2019-01-03	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470949	SCV002767438	pathogenic	Polycystic kidney disease, adult type	2022-02-02	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with polycystic kidney disease 1 (MIM#173900). (I) 0107 - This gene is associated with autosomal dominant disease. Polycystic kidney disease 1 (MIM#173900) is predominantly caused by monoallelic variants, with rare reports of biallelic variants causing disease (OMIM). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported at least ten families with autosomal dominant polycystic kidney disease (ClinVar, PKD database mayo clinic, PMID: 31740684). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Athena Diagnostics	RCV000681754	SCV002771591	pathogenic	not provided	2022-04-05	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has been identified in at least one individual with clinical features associated with this gene. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Fulgent Genetics, Fulgent Genetics	RCV002470949	SCV002784609	pathogenic	Polycystic kidney disease, adult type	2024-02-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000681754	SCV003798703	pathogenic	not provided	2023-02-02	criteria provided, single submitter	clinical testing	Frameshift 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: 34733539, 31740684, 30586318, 11115377)
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV002470949	SCV005184232	pathogenic	Polycystic kidney disease, adult type	2024-07-19	criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS4_Supporting+PP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002470949	SCV006071108	pathogenic	Polycystic kidney disease, adult type	2025-03-17	criteria provided, single submitter	clinical testing	Variant summary: PKD1 c.2085dupC (p.Ala696ArgfsX18) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 139288 control chromosomes. c.2085dupC has been reported in the literature in at-least one heterozygous individual affected with Polycystic kidney disease with a family history for the disease (example: Topak_2024). The following publication has been ascertained in the context of this evaluation (PMID: 37078890). ClinVar contains an entry for this variant (Variation ID: 562308). Based on the evidence outlined above, the variant was classified as pathogenic.
Gharavi Laboratory, Columbia University	RCV000681754	SCV000809212	pathogenic	not provided	2018-09-16	no assertion criteria provided	research