Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001044417 | SCV001208215 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2025-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 555 of the AXIN2 protein (p.Cys555Trp). This variant is present in population databases (rs562421443, gnomAD 0.01%). 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: 842068). 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 AXIN2 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. |
| Gene |
RCV001759759 | SCV001987596 | uncertain significance | not provided | 2019-07-16 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002400255 | SCV002708415 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-08 | criteria provided, single submitter | clinical testing | The p.C555W variant (also known as c.1665C>G), located in coding exon 5 of the AXIN2 gene, results from a C to G substitution at nucleotide position 1665. The cysteine at codon 555 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mayo Clinic Laboratories, |
RCV001759759 | SCV004224426 | uncertain significance | not provided | 2022-03-09 | criteria provided, single submitter | clinical testing | BP4 |