Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000549058 | SCV000639216 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2024-09-12 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 319 of the AXIN2 protein (p.Val319Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 464651). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 |
RCV001557179 | SCV001778896 | uncertain significance | not provided | 2023-11-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002384133 | SCV002694635 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-29 | criteria provided, single submitter | clinical testing | The p.V319I variant (also known as c.955G>A), located in coding exon 2 of the AXIN2 gene, results from a G to A substitution at nucleotide position 955. The valine at codon 319 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001557179 | SCV002774430 | uncertain significance | not provided | 2024-10-15 | criteria provided, single submitter | clinical testing | The AXIN2 c.955G>A (p.Val319Ile) 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 (2/279964 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 benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Fulgent Genetics, |
RCV002506335 | SCV002814878 | uncertain significance | Oligodontia-cancer predisposition syndrome; Colorectal cancer | 2022-05-31 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004568818 | SCV005053235 | uncertain significance | Colorectal cancer | 2023-11-13 | criteria provided, single submitter | clinical testing |