Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569570 | SCV000671625 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-30 | criteria provided, single submitter | clinical testing | The p.P356S variant (also known as c.1066C>T), located in coding exon 11 of the POLE gene, results from a C to T substitution at nucleotide position 1066. The proline at codon 356 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Laboratory for Molecular Medicine, |
RCV000613178 | SCV000731491 | uncertain significance | not specified | 2017-04-19 | criteria provided, single submitter | clinical testing | The p.Pro356Ser variant in POLE has been reported as a somatic variant in a colo rectal carcinoma of 1 German individual (Stenzinger 2014) and was absent from la rge population studies. Computational prediction tools and conservation analysis suggest that the p.Pro356Ser variant may impact the protein, though this inform ation is not predictive enough to determine pathogenicity. In summary, the clini cal significance of the p.Pro356Ser variant is uncertain. |
Invitae | RCV003541200 | SCV001396502 | uncertain significance | not provided | 2022-02-19 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 484542). 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 proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 356 of the POLE protein (p.Pro356Ser). |