ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.7673G>A (p.Arg2558Gln)

dbSNP: rs369677008
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000817649 SCV000958224 uncertain significance Autosomal recessive polycystic kidney disease 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2558 of the PKHD1 protein (p.Arg2558Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs369677008, ExAC 0.01%). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 26695994). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV003233862 SCV003930886 uncertain significance not provided 2023-05-11 criteria provided, single submitter clinical testing Reported as a non-disease causing polymorphism in patients with ARPKD in published literature (Obeidova et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26695994)
Natera, Inc. RCV000817649 SCV001455250 uncertain significance Autosomal recessive polycystic kidney disease 2018-10-23 no assertion criteria provided clinical testing

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