ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.647G>A (p.Cys216Tyr)

dbSNP: rs375346290
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222576 SCV000273446 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-19 criteria provided, single submitter clinical testing The p.C244Y variant (also known as c.731G>A), located in coding exon 9 of the MUTYH gene, results from a G to A substitution at nucleotide position 731. The cysteine at codon 244 is replaced by tyrosine, an amino acid with highly dissimilar properties. In one study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in 1/2512 control individuals from a healthy population database (Rosenthal EA et al. Hum Genet, 2018 Oct;137:795-806). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000560428 SCV000639354 uncertain significance Familial adenomatous polyposis 2 2024-06-04 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 244 of the MUTYH protein (p.Cys244Tyr). This variant is present in population databases (rs375346290, gnomAD 0.0009%). This missense change has been observed in individual(s) with MUTYH-related conditions (PMID: 25368107; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.689G>A (p.Cys230Tyr). ClinVar contains an entry for this variant (Variation ID: 230038). 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 disruptive. 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 Diagnostics, LLC DBA Color Health RCV000222576 SCV000685665 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV000560428 SCV004198855 uncertain significance Familial adenomatous polyposis 2 2023-09-26 criteria provided, single submitter clinical testing

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