Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002049497 | SCV002115007 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 1259 of the PKHD1 protein (p.Asp1259Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). 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 | RCV003264126 | SCV003985301 | uncertain significance | Inborn genetic diseases | 2023-05-09 | criteria provided, single submitter | clinical testing | The c.3775G>A (p.D1259N) alteration is located in exon 32 (coding exon 31) of the PKHD1 gene. This alteration results from a G to A substitution at nucleotide position 3775, causing the aspartic acid (D) at amino acid position 1259 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |