Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001370980 | SCV001567530 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 532 of the AXIN2 protein (p.Glu532Lys). This variant is present in population databases (rs755551294, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1061406). 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 expected to disrupt AXIN2 protein function with a positive 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. |
| Ambry Genetics | RCV002404884 | SCV002709014 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-30 | criteria provided, single submitter | clinical testing | The p.E532K variant (also known as c.1594G>A), located in coding exon 5 of the AXIN2 gene, results from a G to A substitution at nucleotide position 1594. The glutamic acid at codon 532 is replaced by lysine, an amino acid with 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. |
| Baylor Genetics | RCV003473887 | SCV004213053 | uncertain significance | Colorectal cancer | 2023-08-25 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998856 | SCV005624944 | uncertain significance | not provided | 2024-05-06 | criteria provided, single submitter | clinical testing | The AXIN2 c.1594G>A (p.Glu532Lys) variant has not been reported in individuals with AXIN2-related conditions in the published literature. The frequency of this variant in the general population, 0.0000071 (2/282780 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |