Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002264173 | SCV001229663 | uncertain significance | not provided | 2023-01-17 | criteria provided, single submitter | clinical testing | 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt POLE protein function. ClinVar contains an entry for this variant (Variation ID: 858788). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2148 of the POLE protein (p.Cys2148Arg). |
Ce |
RCV002264173 | SCV002545088 | uncertain significance | not provided | 2022-05-01 | criteria provided, single submitter | clinical testing | POLE: PM2 |
Ambry Genetics | RCV002365753 | SCV002659614 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-19 | criteria provided, single submitter | clinical testing | The p.C2148R variant (also known as c.6442T>C), located in coding exon 46 of the POLE gene, results from a T to C substitution at nucleotide position 6442. The cysteine at codon 2148 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV002264173 | SCV004169244 | uncertain significance | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |