Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000226305 | SCV000287557 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2016-03-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 725 of the POLD1 protein (p.Arg725Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. While this variant is not present in population databases (ExAC no frequency), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a POLD1-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"). In summary, this is a missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |