Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022834 | SCV001184615 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-12 | criteria provided, single submitter | clinical testing | The c.4647delC variant, located in coding exon 36 of the POLE gene, results from a deletion of one nucleotide at nucleotide position 4647, causing a translational frameshift with a predicted alternate stop codon (p.K1550Nfs*12). 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 | RCV003769567 | SCV001569167 | pathogenic | not provided | 2022-05-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys1550Asnfs*12) 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: 825067). For these reasons, this variant has been classified as Pathogenic. |