Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010802 | SCV001171050 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-02 | criteria provided, single submitter | clinical testing | The c.1293delG variant, located in coding exon 13 of the POLE gene, results from a deletion of one nucleotide at nucleotide position 1293, causing a translational frameshift with a predicted alternate stop codon (p.K431Nfs*2). 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. |
| Invitae | RCV003658330 | SCV003239805 | pathogenic | not provided | 2022-05-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 818824). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys431Asnfs*2) 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). |