Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478515 | SCV000572909 | uncertain significance | not provided | 2023-01-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26878173, Shah2022[Preprint], 20951805) |
| Labcorp Genetics |
RCV000478515 | SCV000653027 | uncertain significance | not provided | 2024-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 370 of the POLE protein (p.Pro370Thr). This variant is present in population databases (rs576578672, gnomAD 0.04%). 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: 423238). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV000574504 | SCV000671466 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-18 | criteria provided, single submitter | clinical testing | The p.P370T variant (also known as c.1108C>A), located in coding exon 12 of the POLE gene, results from a C to A substitution at nucleotide position 1108. The proline at codon 370 is replaced by threonine, an amino acid with highly 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. |
| Fulgent Genetics, |
RCV000763815 | SCV000894732 | uncertain significance | Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000574504 | SCV002538590 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | curation | |
| St. |
RCV000530755 | SCV003843037 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2023-02-13 | criteria provided, single submitter | clinical testing | The POLE c.1108C>A (p.Pro370Thr) missense change has a maximum founder subpopulation frequency of 0.048% is absent in gnomAD v2.1.1 and is absent in all non-founder subpopulations (https://gnomad.broadinstitute.org). This variant is in the exonuclease domain but does not affect a known hotspot codon. The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with POLE-related disease. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.? |
| Baylor Genetics | RCV000530755 | SCV004203518 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2024-02-11 | criteria provided, single submitter | clinical testing |