Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024360 | SCV001186360 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-15 | criteria provided, single submitter | clinical testing | The p.E1881* variant (also known as c.5641G>T), located in coding exon 41 of the POLE gene, results from a G to T substitution at nucleotide position 5641. This changes the amino acid from a glutamic acid to a stop codon within coding exon 41. 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 | RCV003658105 | SCV003196328 | pathogenic | not provided | 2022-05-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 825869). 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.Glu1881*) 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). |