ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.1651T>C (p.Cys551Arg)

gnomAD frequency: 0.00001  dbSNP: rs730881398
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159775 SCV000209797 uncertain significance not provided 2023-03-20 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
Invitae RCV000229143 SCV000288671 uncertain significance Oligodontia-cancer predisposition syndrome 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 551 of the AXIN2 protein (p.Cys551Arg). This variant is present in population databases (rs730881398, gnomAD 0.003%). 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: 182006). 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, Fulgent Genetics RCV000765387 SCV000896660 uncertain significance Oligodontia-cancer predisposition syndrome; Carcinoma of colon 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002399582 SCV002704171 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The p.C551R variant (also known as c.1651T>C), located in coding exon 5 of the AXIN2 gene, results from a T to C substitution at nucleotide position 1651. The cysteine at codon 551 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is well 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.
Preventiongenetics, part of Exact Sciences RCV003398821 SCV004110246 uncertain significance AXIN2-related condition 2023-07-20 criteria provided, single submitter clinical testing The AXIN2 c.1651T>C variant is predicted to result in the amino acid substitution p.Cys551Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-63533503-A-G). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/182006/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003474819 SCV004213058 uncertain significance Colorectal cancer 2023-08-15 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV000229143 SCV001749696 not provided Oligodontia-cancer predisposition syndrome no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 10-06-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.