ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.890G>A (p.Cys297Tyr) (rs879254257)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236614 SCV000293990 likely pathogenic not provided 2016-02-22 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.890G>A at the cDNA level, p.Cys297Tyr (C297Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGC>TAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MUTYH Cys297Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Cysteine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MUTYH Cys297Tyr occurs at a position that is conserved across species and is located in the within FeS cluster (Ruggieri 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence, we consider MUTYH Cys297Tyr to be a likely pathogenic variant.
Invitae RCV000813716 SCV000954086 uncertain significance MYH-associated polyposis 2019-01-29 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 297 of the MUTYH protein (p.Cys297Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 29371908). This variant is also known as c.881G>A (p.Cys294Tyr) in the literature. ClinVar contains an entry for this variant (Variation ID: 246433). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV001186972 SCV001353607 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-25 criteria provided, single submitter clinical testing

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