Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484801 | SCV000564564 | uncertain significance | not provided | 2016-10-04 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.1396A>G at the cDNA level, p.Met466Val (M466V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Met466Val 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 Methionine and Valine share similar properties, this is considered a conservative amino acid substitution. APC Met466Val occurs at a position that is conserved across species and is located in the armadillo region (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Met466Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000565633 | SCV000667703 | likely benign | Hereditary cancer-predisposing syndrome | 2021-10-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Invitae | RCV003535742 | SCV000822518 | uncertain significance | Familial adenomatous polyposis 1 | 2023-05-07 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs781364007, gnomAD 0.02%). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 466 of the APC protein (p.Met466Val). This variant has not been reported in the literature in individuals affected with APC-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. ClinVar contains an entry for this variant (Variation ID: 418009). |
Baylor Genetics | RCV002526511 | SCV004204564 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-30 | criteria provided, single submitter | clinical testing | |
3DMed Clinical Laboratory Inc | RCV000677766 | SCV000803922 | uncertain significance | Colorectal cancer | 2018-04-21 | no assertion criteria provided | clinical testing |