Submissions for variant NM_004655.4(AXIN2):c.721T>G (p.Cys241Gly)

gnomAD frequency: 0.00001  dbSNP: rs370549410

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226291	SCV000288719	uncertain significance	Oligodontia-cancer predisposition syndrome	2024-01-14	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 241 of the AXIN2 protein (p.Cys241Gly). This variant is present in population databases (rs370549410, gnomAD 0.04%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 240028). 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.
Ambry Genetics	RCV001026173	SCV001188499	benign	Hereditary cancer-predisposing syndrome	2024-03-28	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001546012	SCV001765449	uncertain significance	not provided	2023-12-21	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with ovarian cancer (PMID: 30093976); This variant is associated with the following publications: (PMID: Drasin2023[Case report], 30093976)
Sema4, Sema4	RCV001026173	SCV002537220	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-20	criteria provided, single submitter	curation
Baylor Genetics	RCV004567747	SCV005053194	uncertain significance	Colorectal cancer	2024-01-10	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001546012	SCV001809391	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001546012	SCV001924419	likely benign	not provided		no assertion criteria provided	clinical testing