Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003655029 | SCV000653293 | pathogenic | not provided | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg150*) in the POLE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POLE are known to be pathogenic (PMID: 23230001, 25948378, 30503519). This variant is present in population databases (rs775815329, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 473667). For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000524885 | SCV000785690 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2017-11-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001022564 | SCV001184318 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-04-25 | criteria provided, single submitter | clinical testing | The p.R150* variant (also known as c.448C>T), located in coding exon 6 of the POLE gene, results from a C to T substitution at nucleotide position 448. This changes the amino acid from an arginine to a stop codon within coding exon 6. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of POLE has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |