Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000585603 | SCV000692765 | likely pathogenic | not provided | 2017-08-01 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000611235 | SCV000731465 | uncertain significance | not specified | 2017-04-21 | criteria provided, single submitter | clinical testing | The p.Gln2208fs variant in POLE has not been previously reported in individuals with colorectal cancer and was absent from large population studies. This varian t is predicted to cause a frameshift, which alters the protein?s amino acid sequ ence beginning at position 2208 and leads to a premature termination codon 4 ami no acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Although this variant is expected to impact the protein, the PO LE gene has not yet been widely studied in patients (to date, virtually all vari ants reported in patients with colorectal cancer represent missense changes). In summary, the clinical significance of the p.Gln2208fs variant is uncertain. |
| Ambry Genetics | RCV001025467 | SCV001187662 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-04 | criteria provided, single submitter | clinical testing | The c.6623delA variant, located in coding exon 47 of the POLE gene, results from a deletion of one nucleotide at nucleotide position 6623, causing a translational frameshift with a predicted alternate stop codon (p.Q2208Rfs*4). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of POLE has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000585603 | SCV002197580 | pathogenic | not provided | 2024-06-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln2208Argfs*4) in the POLE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLE are known to be pathogenic (PMID: 23230001, 25948378, 30503519). This variant is not present in population databases (gnomAD no frequency). 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: 493130). For these reasons, this variant has been classified as Pathogenic. |