ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.544A>G (p.Met182Val)

gnomAD frequency: 0.00004  dbSNP: rs976524379
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000640264 SCV000761853 uncertain significance Oligodontia-cancer predisposition syndrome 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 182 of the AXIN2 protein (p.Met182Val). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 533235). 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 expected to disrupt AXIN2 protein function with a positive 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 RCV001024121 SCV001186083 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-06 criteria provided, single submitter clinical testing The p.M182V variant (also known as c.544A>G), located in coding exon 1 of the AXIN2 gene, results from an A to G substitution at nucleotide position 544. The methionine at codon 182 is replaced by valine, 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 highly conserved in available vertebrate species. 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.
GeneDx RCV001731830 SCV001983024 uncertain significance not provided 2024-01-18 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; Observed in 0/57 cases and in 1/1358 controls in a melanoma and multiple primary cancer study (PMID: 29641532); This variant is associated with the following publications: (PMID: 29641532)
Baylor Genetics RCV003472029 SCV004213061 uncertain significance Colorectal cancer 2023-08-15 criteria provided, single submitter clinical testing

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