Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000235266 | SCV000293742 | uncertain significance | not provided | 2024-03-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23359684, 25228659, 24265153, 26110843, 28912153, 32546565) |
| Labcorp Genetics |
RCV000235266 | SCV000543923 | uncertain significance | not provided | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1967 of the POLE protein (p.Ala1967Val). This variant is present in population databases (rs201273415, 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: 246263). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Prevention |
RCV004529416 | SCV000806821 | uncertain significance | POLE-related disorder | 2023-05-23 | criteria provided, single submitter | clinical testing | The POLE c.5900C>T variant is predicted to result in the amino acid substitution p.Ala1967Val. To our knowledge, this variant has not been reported in individuals with POLE-related disease. This variant is reported in 0.052% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-133210876-G-A) and has conflicting interpretations in ClinVar of uncertain and likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/246263/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Mendelics | RCV000461742 | SCV001138859 | likely benign | Colorectal cancer, susceptibility to, 12 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV002257607 | SCV002536903 | likely benign | Hereditary cancer-predisposing syndrome | 2021-04-19 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002257607 | SCV005478812 | likely benign | Hereditary cancer-predisposing syndrome | 2024-10-17 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV005008211 | SCV005633675 | uncertain significance | Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency | 2023-12-28 | criteria provided, single submitter | clinical testing |