Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023910 | SCV001185853 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-20 | criteria provided, single submitter | clinical testing | The c.5316_5317delTG variant, located in coding exon 39 of the POLE gene, results from a deletion of two nucleotides at nucleotide positions 5316 to 5317, causing a translational frameshift with a predicted alternate stop codon (p.G1773Sfs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function via haploinsufficiency in 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 | RCV003769587 | SCV001490451 | pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly1773Serfs*11) 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: 825642). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |