Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709241 | SCV000838672 | uncertain significance | Familial colorectal cancer | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003656132 | SCV001392627 | pathogenic | not provided | 2023-06-25 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.006%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 584829). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This sequence change creates a premature translational stop signal (p.Arg2145*) 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). |
| Ambry Genetics | RCV002360841 | SCV002659588 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-12 | criteria provided, single submitter | clinical testing | The p.R2145* variant (also known as c.6433C>T), located in coding exon 46 of the POLE gene, results from a C to T substitution at nucleotide position 6433. This changes the amino acid from an arginine to a stop codon within coding exon 46. 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. |