Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000549767 | SCV000639133 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2024-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 651 of the AXIN2 protein (p.Ser651Trp). This variant is not present in population databases (gnomAD no frequency). 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: 464586). 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. |
| Sema4, |
RCV002257799 | SCV002537123 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV002257799 | SCV002718805 | likely benign | Hereditary cancer-predisposing syndrome | 2023-06-07 | 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. |
| ARUP Laboratories, |
RCV003114662 | SCV003800051 | uncertain significance | not provided | 2022-03-18 | criteria provided, single submitter | clinical testing | The AXIN2 c.1952C>G; p.Ser651Trp variant (rs74006838), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 464586). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 651 is weakly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.184). Due to limited information, the clinical significance of the p.Ser651Trp variant is uncertain at this time. |
| Baylor Genetics | RCV003476266 | SCV004213023 | uncertain significance | Colorectal cancer | 2023-09-20 | criteria provided, single submitter | clinical testing |