Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001874106 | SCV002120299 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-07-19 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with cysteine at codon 362 of the PKHD1 protein (p.Phe362Cys). The phenylalanine residue is weakly conserved and there is a large physicochemical difference between phenylalanine and cysteine. |