Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482453 | SCV000569644 | uncertain significance | not provided | 2016-03-17 | criteria provided, single submitter | clinical testing | This variant is denoted POLE c.4873C>G at the cDNA level, p.Gln1625Glu (Q1625E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAG>GAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. POLE Gln1625Glu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Glutamic Acid differ in some properties, this is considered a semi-conservative amino acid substitution. POLE Gln1625Glu occurs at a position that is conserved across species and is not located in a known functional domain (Tahirov 2009, Preston 2010, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether POLE Gln1625Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Ambry Genetics | RCV004659058 | SCV005154274 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-17 | criteria provided, single submitter | clinical testing | The p.Q1625E variant (also known as c.4873C>G), located in coding exon 37 of the POLE gene, results from a C to G substitution at nucleotide position 4873. The glutamine at codon 1625 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |