Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000814434 | SCV000954844 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2021-02-19 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 904 of the POLD1 protein (p.Ala904Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POLD1-related disease. |
| Ambry Genetics | RCV002433975 | SCV002745013 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-14 | criteria provided, single submitter | clinical testing | The p.A904S variant (also known as c.2710G>T), located in coding exon 20 of the POLD1 gene, results from a G to T substitution at nucleotide position 2710. The alanine at codon 904 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |