Total submissions: 5
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. |
Gene |
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, |
RCV002461189 | SCV004227257 | uncertain significance | not provided | 2023-01-18 | criteria provided, single submitter | clinical testing | PM2 |
Natera, |
RCV000462402 | SCV001463512 | uncertain significance | Autosomal recessive polycystic kidney disease | 2017-08-10 | no assertion criteria provided | clinical testing |