ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1717G>T (p.Gly573Trp)

gnomAD frequency: 0.00019  dbSNP: rs143867809
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462402 SCV000545838 uncertain significance Autosomal recessive polycystic kidney disease 2022-06-24 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 573 of the PKHD1 protein (p.Gly573Trp). This variant is present in population databases (rs143867809, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 406883). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 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 RCV002461189 SCV002757192 uncertain significance not provided 2022-11-26 criteria provided, single submitter clinical testing Reported with a pathogenic variant on the opposite allele (in trans) in a fetus with cardiac abnormalities as secondary findings in published literature; however, no clinical information on renal status was provided (Becher et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32304219)
Ambry Genetics RCV002525547 SCV003678638 uncertain significance Inborn genetic diseases 2021-12-03 criteria provided, single submitter clinical testing The c.1717G>T (p.G573W) alteration is located in exon 19 (coding exon 18) of the PKHD1 gene. This alteration results from a G to T substitution at nucleotide position 1717, causing the glycine (G) at amino acid position 573 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV002461189 SCV004227257 uncertain significance not provided 2023-01-18 criteria provided, single submitter clinical testing PM2
Natera, Inc. RCV000462402 SCV001463512 uncertain significance Autosomal recessive polycystic kidney disease 2017-08-10 no assertion criteria provided clinical testing

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