Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701227 | SCV000830018 | uncertain significance | Autosomal recessive polycystic kidney disease | 2018-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with arginine at codon 297 of the PKHD1 protein (p.Cys297Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PKHD1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Cys297Ser) has been reported in trans with a pathogenic variant in an individual affected with autosomal recessive polycystic kidney disease (PMID: 27577217). 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. |