ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.377G>A (p.Arg126Gln) (rs587781444)

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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 RCV000129359 SCV000184123 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-07 criteria provided, single submitter clinical testing The p.R126Q variant (also known as c.377G>A), located in coding exon 4 of the MUTYH gene, results from a G to A substitution at nucleotide position 377. The arginine at codon 126 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported (designated as c.326G>A) in an individual with polyposis who was also heterozygous for an MUTYH mutation; however, phase of the two alterations was not confirmed (Guarinos C et al. Clin. Cancer Res. 2014 Mar;20:1158-68). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000460472 SCV000545783 uncertain significance MYH-associated polyposis 2020-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 126 of the MUTYH protein (p.Arg126Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs587781444, ExAC 0.02%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 141028). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590181 SCV000697686 uncertain significance not provided 2016-03-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129359 SCV001357388 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-20 criteria provided, single submitter clinical testing

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