Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003541149 | SCV001382445 | uncertain significance | not provided | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change affects codon 1651 of the POLE mRNA. It is a 'silent' change, meaning that it does not 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 (no rsID available, gnomAD 0.003%). 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: 941194). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). 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 | RCV002339546 | SCV002641717 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-25 | criteria provided, single submitter | clinical testing | The c.4953G>A variant (also known as p.R1651R), located in coding exon 38 of the POLE gene, results from a G to A substitution at nucleotide position 4953. This nucleotide substitution does not change the at codon 1651. However, this change occurs in the first base pair of coding exon 38, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |