Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003541312 | SCV001409954 | uncertain significance | not provided | 2022-08-21 | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 963205). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1687 of the POLE protein (p.Ser1687Thr). |
Ambry Genetics | RCV002339656 | SCV002643564 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-02 | criteria provided, single submitter | clinical testing | The p.S1687T variant (also known as c.5059T>A), located in coding exon 38 of the POLE gene, results from a T to A substitution at nucleotide position 5059. The serine at codon 1687 is replaced by threonine, an amino acid with similar 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. |