Submissions for variant NM_001009944.3(PKD1):c.10540C>T (p.Gln3514Ter)

dbSNP: rs1567159623

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756524	SCV000884359	pathogenic	not provided	2017-12-21	criteria provided, single submitter	clinical testing	The PKD1 c.10540C>T, p.Gln3514Ter variant has been reported in multiple individuals diagnosed with autosomal polycystic kidney disease (Audrezet 2012, Peral 1997). It is not observed in the dbSNP variant databse, in the ClinVar database, or in the general population databases, such as the 1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database. The 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 p.Gln3514Ter 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. Peral B et al. Identification of mutations in the duplicated region of the polycystic kidney disease 1 gene (PKD1) by a novel approach. Am J Hum Genet. 1997; 60(6):1399-410.
PreventionGenetics, part of Exact Sciences	RCV004723153	SCV005340143	pathogenic	PKD1-related disorder	2024-05-31	no assertion criteria provided	clinical testing	The PKD1 c.10540C>T variant is predicted to result in premature protein termination (p.Gln3514*). This variant has been reported in an individual with Polycystic kidney disease (Reported as p.Gln3513*, Peral et al. 1997. PubMed ID: 9199561). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in PKD1 are expected to be pathogenic. This variant is interpreted as pathogenic.