ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.12683G>C (p.Arg4228Pro)

dbSNP: rs1064797205
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000488250 SCV000575027 likely pathogenic not provided 2016-11-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005010402 SCV005638994 likely pathogenic Polycystic kidney disease, adult type 2024-02-14 criteria provided, single submitter clinical testing
Molecular Genetics, Royal Melbourne Hospital RCV005250060 SCV005900432 likely pathogenic Autosomal dominant polycystic kidney disease 2025-01-07 criteria provided, single submitter clinical testing This sequence change in PKD1 is predicted to replace arginine with proline at codon 4228, p.(Arg4228Pro). The arginine residue is highly conserved (100 vertebrates, Multiz Alignments), and is located in the coiled-coil domain. There is a large physicochemical difference between arginine and proline. This variant is absent from the population database gnomAD v4.1. This variant has been reported in four unrelated probands with autosomal dominant polycystic kidney disease (ADPKD; PMID: 19686598; ClinVar ID: SCV000575027.6; ADPKD Variant Database). At least one individual with this variant had a family history of ADPKD and displayed multiple renal cysts on ultrasound, which is highly specific for ADPKD (Royal Melbourne Hospital). Computational evidence predicts a benign effect for the missense substitution (REVEL = 0.158) and has an uninformative predicted impact on splicing (SpliceAI) for the nucleotide change. Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.7.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PP4_Strong, PS4, PM2_Supporting, BP4

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