Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003654310 | SCV000544009 | uncertain significance | not provided | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1810 of the POLE protein (p.His1810Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 25058500). This variant is also known as c.5473A>T. ClinVar contains an entry for this variant (Variation ID: 405694). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt POLE protein function with a negative predictive value of 80%. 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. |
| Mendelics | RCV000709248 | SCV000838679 | likely benign | Familial colorectal cancer | 2024-04-09 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003654310 | SCV005325001 | uncertain significance | not provided | 2023-06-16 | 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; Observed in individuals with a personal and/or family history of colorectal cancer (Esteban-Jurado et al., 2015); This variant is associated with the following publications: (PMID: 25058500) |