Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002785859 | SCV003024519 | uncertain significance | Autosomal recessive polycystic kidney disease | 2022-06-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 2169 of the PKHD1 protein (p.Cys2169Tyr). This variant is present in population databases (rs757717736, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. 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. |
| Ambry Genetics | RCV003167759 | SCV003909852 | uncertain significance | Inborn genetic diseases | 2023-03-13 | criteria provided, single submitter | clinical testing | The c.6506G>A (p.C2169Y) alteration is located in exon 40 (coding exon 39) of the PKHD1 gene. This alteration results from a G to A substitution at nucleotide position 6506, causing the cysteine (C) at amino acid position 2169 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |