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

gnomAD frequency: 0.00001  dbSNP: rs730881398

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159775	SCV000209797	uncertain significance	not provided	2024-01-09	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
Labcorp Genetics (formerly Invitae), Labcorp	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	RCV004528901	SCV004110246	uncertain significance	AXIN2-related disorder	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.