Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003088293 | SCV003479103 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1887 of the PKHD1 protein (p.Glu1887Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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 not 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 | RCV003274229 | SCV003958136 | uncertain significance | Inborn genetic diseases | 2023-03-20 | criteria provided, single submitter | clinical testing | The c.5660A>C (p.E1887A) alteration is located in exon 35 (coding exon 34) of the PKHD1 gene. This alteration results from a A to C substitution at nucleotide position 5660, causing the glutamic acid (E) at amino acid position 1887 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |