ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.6115C>T (p.Gln2039Ter)

dbSNP: rs755747732
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV002225209 SCV002503773 pathogenic Polycystic kidney disease, adult type 2023-03-30 criteria provided, single submitter clinical testing This sequence change creates a premature termination codon at position 2039 in exon 15 (of 46) of PKD1 (p.Gln2039*). It is expected to result in an absent or disrupted protein product in a gene where loss-of-function is a well-established mechanism of disease (PVS1). The variant is absent in a large population cohort (gnomAD v2.1 - PM2). Including a patient in the laboratory database, there are at least four cases diagnosed with polycystic kidney disease with this variant (PMID: 11012875, 22508176, 30333007 - PS4_Supporting). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2, PS4_Supporting.
Fulgent Genetics, Fulgent Genetics RCV002225209 SCV002811567 pathogenic Polycystic kidney disease, adult type 2021-10-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV003089197 SCV003590912 pathogenic Inborn genetic diseases 2021-11-18 criteria provided, single submitter clinical testing The c.6115C>T (p.Q2039*) alteration, located in exon 15 (coding exon 15) of the PKD1 gene, consists of a C to T substitution at nucleotide position 6115. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 2039. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in multiple patients with autosomal dominant polycystic kidney disease (Phakdeekitcharoen, 2000; Audrézet, 2012; Hwang, 2016; He, 2018; Kim, 2019). Based on the available evidence, this alteration is classified as pathogenic.
GeneDx RCV004784041 SCV005396007 pathogenic not provided 2024-05-06 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: 25525159, 26453610, 11012875, 30333007, 36938073, 22508176, 31740684)

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