Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002018904 | SCV002262812 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-03-31 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with PKHD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with asparagine at codon 3538 of the PKHD1 protein (p.Ile3538Asn). The isoleucine residue is moderately conserved and there is a large physicochemical difference between isoleucine and asparagine. 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. 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. |