ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.6384C>G (p.Asn2128Lys)

dbSNP: rs1247882278
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV002221399 SCV002498641 uncertain significance Polycystic kidney disease, adult type 2023-03-30 criteria provided, single submitter clinical testing This sequence change in PKD1 is predicted to replace asparagine with lysine at codon 2128 (p.(Asn2128Lys)). The asparagine residue is evolutionarily conserved (100 vertebrates, UCSC), and is located in the PKD 17 domain. There is a moderate physicochemical difference between asparagine and lysine. This variant is absent from gnomAD v2.1 and v3.1. To our knowledge, this variant has not been reported in the literature or in relevant databases in any individuals with polycystic kidney disease. It has been identified in an individual with a clinical diagnosis of autosomal dominant polycystic kidney disease (ADPKD, Royal Melbourne Hospital). Multiple lines of computational evidence predict a deleterious effect for the missense substitution (5/6 algorithms). The same amino acid change (p.Asn2128Lys), resulting from a different nucleotide change c.6384C>A, has been reported in a single patient with ADPKD and as a somatic second hit in a kidney cyst (PMID: 25333066, 30042192). Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PS4_Supporting, PM2_Supporting, PP3.
GeneDx RCV004774632 SCV005383402 uncertain significance not provided 2024-02-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002221399 SCV005641314 likely pathogenic Polycystic kidney disease, adult type 2024-05-14 criteria provided, single submitter clinical testing

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