ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.1375C>T (p.Arg459Cys)

gnomAD frequency: 0.00001  dbSNP: rs777680532
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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 RCV000640165 SCV000761753 uncertain significance Oligodontia-cancer predisposition syndrome 2024-09-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 459 of the AXIN2 protein (p.Arg459Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 533142). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV002386049 SCV002697257 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-26 criteria provided, single submitter clinical testing The p.R459C variant (also known as c.1375C>T), located in coding exon 5 of the AXIN2 gene, results from a C to T substitution at nucleotide position 1375. The arginine at codon 459 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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.
Baylor Genetics RCV003472009 SCV004213052 uncertain significance Colorectal cancer 2023-08-25 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005019062 SCV005650974 uncertain significance Oligodontia-cancer predisposition syndrome; Colorectal cancer 2024-04-29 criteria provided, single submitter clinical testing

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