Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656512 | SCV001382715 | uncertain significance | not provided | 2020-12-09 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 941407). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 1445 of the POLE protein (p.Cys1445Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Ambry Genetics | RCV003380882 | SCV004089327 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | The p.C1445Y variant (also known as c.4334G>A), located in coding exon 34 of the POLE gene, results from a G to A substitution at nucleotide position 4334. The cysteine at codon 1445 is replaced by tyrosine, 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. |