Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656172 | SCV001199157 | uncertain significance | not provided | 2019-12-15 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with POLE-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with tyrosine at codon 1385 of the POLE protein (p.Asn1385Tyr). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and tyrosine. |
| Ambry Genetics | RCV002327248 | SCV002627471 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-21 | criteria provided, single submitter | clinical testing | The p.N1385Y variant (also known as c.4153A>T), located in coding exon 33 of the POLE gene, results from an A to T substitution at nucleotide position 4153. The asparagine at codon 1385 is replaced by tyrosine, an amino acid with dissimilar 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. |