Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000687877 | SCV000815468 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2024-10-15 | 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 376 of the AXIN2 protein (p.Ser376Trp). This variant is present in population databases (no rsID available, 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: 567715). 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. |
| Ambry Genetics | RCV002442427 | SCV002753666 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-06 | criteria provided, single submitter | clinical testing | The p.S376W variant (also known as c.1127C>G), located in coding exon 4 of the AXIN2 gene, results from a C to G substitution at nucleotide position 1127. The serine at codon 376 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
| St. |
RCV000687877 | SCV003843183 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2022-12-07 | criteria provided, single submitter | clinical testing | The AXIN2 c.1127C>G (p.Ser376Trp) change has a maximum subpopulation frequency of 0.011% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in the literature in individuals with oligodontia-cancer predisposition syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Prevention |
RCV004527740 | SCV004109474 | uncertain significance | AXIN2-related disorder | 2023-06-13 | criteria provided, single submitter | clinical testing | The AXIN2 c.1127C>G variant is predicted to result in the amino acid substitution p.Ser376Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-63534394-G-C). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/567715/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Gene |
RCV004719945 | SCV005326053 | uncertain significance | not provided | 2024-02-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15735151) |