ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1444G>A (p.Val482Met) (rs587781385)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129217 SCV000183968 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-30 criteria provided, single submitter clinical testing The p.V496M variant (also known as c.1486G>A), located in coding exon 15 of the MUTYH gene, results from a G to A substitution at nucleotide position 1486. The valine at codon 496 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and methionine is the reference amino acid in other 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.
Invitae RCV000226351 SCV000285934 uncertain significance MYH-associated polyposis 2019-08-27 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 496 of the MUTYH protein (p.Val496Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 140942). 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 tolerated, but these predictions have not been confirmed by published functional studies. Furthermore, the methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.
Counsyl RCV000226351 SCV000487318 uncertain significance MYH-associated polyposis 2015-12-13 criteria provided, single submitter clinical testing

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