Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000550906 | SCV000646630 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2017-03-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 1017 of the POLD1 protein (p.Thr1017Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. While this variant is not present in population databases, 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 individuals 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: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |