Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000230145 | SCV000288686 | uncertain significance | Oligodontia-cancer predisposition syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 667 of the AXIN2 protein (p.Ser667Asn). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 240004). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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. |
Fulgent Genetics, |
RCV000765384 | SCV000896657 | uncertain significance | Oligodontia-cancer predisposition syndrome; Carcinoma of colon | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001014047 | SCV001174706 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-30 | criteria provided, single submitter | clinical testing | The p.S667N variant (also known as c.2000G>A), located in coding exon 7 of the AXIN2 gene, results from a G to A substitution at nucleotide position 2000. The serine at codon 667 is replaced by asparagine, an amino acid with highly similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is poorly 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. |
Gene |
RCV001551935 | SCV001772542 | uncertain significance | not provided | 2019-04-15 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV003475824 | SCV004213042 | uncertain significance | Colorectal cancer | 2023-09-01 | criteria provided, single submitter | clinical testing |