Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000606137 | SCV000731272 | uncertain significance | not specified | 2016-11-22 | criteria provided, single submitter | clinical testing | The c.1107-3C>T variant in POLE has not been previously reported in individuals with colorectal cancer or in large population studies. This variant is located i n the 3' splice region. Computational tools do not suggest an impact to splicing . However, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the c.1107-3C>T variant is uncertain. |
Invitae | RCV003767740 | SCV000772839 | uncertain significance | not provided | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the POLE gene. It does not directly change the encoded amino acid sequence of the POLE protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369572563, gnomAD 0.0009%). 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: 517160). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV001009907 | SCV001170035 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-21 | criteria provided, single submitter | clinical testing | The c.1107-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 12 in the POLE gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP splice site prediction tool, this alteration is not predicted to have any significant effect on this splice acceptor site while the ESEfinder splice site prediction tool predicts a slight weakening in the native splice acceptor site efficiency; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |