Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001940485 | SCV002192240 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-04-03 | criteria provided, single submitter | clinical testing | 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 expected to disrupt PKHD1 protein function. 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 phenylalanine with isoleucine at codon 2477 of the PKHD1 protein (p.Phe2477Ile). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and isoleucine. |