Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003656542 | SCV001387332 | uncertain significance | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1054 of the POLE protein (p.Ile1054Val). 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: 945046). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on POLE protein function. 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 | RCV002322044 | SCV002608481 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-28 | criteria provided, single submitter | clinical testing | The p.I1054V variant (also known as c.3160A>G), located in coding exon 26 of the POLE gene, results from an A to G substitution at nucleotide position 3160. The isoleucine at codon 1054 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003918783 | SCV004732989 | uncertain significance | POLE-related condition | 2024-01-12 | criteria provided, single submitter | clinical testing | The POLE c.3160A>G variant is predicted to result in the amino acid substitution p.Ile1054Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been classified as variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/945046/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |