ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.12326_12335del (p.Arg4109fs)

dbSNP: rs2091440547
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research RCV001249166 SCV001422371 likely pathogenic not provided 2019-01-01 criteria provided, single submitter clinical testing
Molecular Genetics, Royal Melbourne Hospital RCV002225130 SCV002503608 likely pathogenic Polycystic kidney disease, adult type 2023-03-30 criteria provided, single submitter clinical testing This sequence change is a deletion of 10 bp in exon 45 (of 46) of PKD1 that is predicted to create a premature termination codon at position 4,194 (p.Arg4109Profs*86). While this is not anticipated to result in nonsense mediated decay, it is expected to remove the last 209 amino acids, including the coiled-coil domain. This domain is critical for PKD1 function and required for interaction with PKD2 (PMID: 9192675, 25574838). Loss of function variants have been reported downstream of this variant (PVS1_Strong; ClinVar). The variant is absent in a large population cohort (PM2; gnomAD v2.1), and has been reported in at least one individual with a clinical diagnosis of autosomal dominant polycystic kidney disease (PS4_Supporting; Genome One). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1_Strong, PM2, PS4_Supporting.

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