Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024534 | SCV001186565 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-26 | criteria provided, single submitter | clinical testing | The c.579-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 7 in the POLE gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003769595 | SCV001561937 | likely benign | not provided | 2023-11-30 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV003151264 | SCV003839905 | uncertain significance | not specified | 2022-09-15 | no assertion criteria provided | clinical testing | DNA sequence analysis of the POLE gene demonstrated a sequence change in intron 6, c.579-3T>C. This change does not appear to have been previously described in individuals with POLE-related disorders and has also not been described in population databases such as ExAC and gnomAD. This sequence change is not predicted to have a deleterious effect on splicing based on in-silico splice prediction programs. It is possible that this sequence change represents a benign sequence change in the POLE gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined. |