Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001242165 | SCV001415235 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2022-07-18 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 1356 of the POLE protein (p.His1356Asp). This variant is present in population databases (rs557732922, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 967289). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV002322150 | SCV002631976 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-01 | criteria provided, single submitter | clinical testing | The p.H1356D variant (also known as c.4066C>G), located in coding exon 32 of the POLE gene, results from a C to G substitution at nucleotide position 4066. The histidine at codon 1356 is replaced by aspartic acid, 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. |