ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.920G>A (p.Arg307Gln) (rs140156029)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129507 SCV000184280 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-02 criteria provided, single submitter clinical testing The p.R307Q variant (also known as c.920G>A), located in coding exon 10 of the MUTYH gene, results from a G to A substitution at nucleotide position 920. The arginine at codon 307 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well 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.
Invitae RCV000467096 SCV000545750 uncertain significance MYH-associated polyposis 2020-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 307 of the MUTYH protein (p.Arg307Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs140156029, ExAC 0.05%). This variant has been observed in individual(s) with breast cancer or an unspecified cancer (PMID: 25186627, 28873162). ClinVar contains an entry for this variant (Variation ID: 141135). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
GeneDx RCV000586807 SCV000567604 uncertain significance not provided 2019-10-10 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in one individual with advanced cancer of unspecified type (Mandelker 2017); This variant is associated with the following publications: (PMID: 28873162, 28944238)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484904 SCV000601661 uncertain significance not specified 2017-06-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000484904 SCV000697713 uncertain significance not specified 2019-05-14 criteria provided, single submitter clinical testing Variant summary: MUTYH c.920G>A (p.Arg307Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 251290 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MUTYH causing MUTYH-associated Polyposis (7.6e-05 vs 0.0046), allowing no conclusion about variant significance. c.920G>A has been reported in the literature in individuals affected with cancer (Tung_2014, Mandelker_2017). These report(s) do not provide unequivocal conclusions about association of the variant with MUTYH-associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Health, Inc RCV000129507 SCV000910765 likely benign Hereditary cancer-predisposing syndrome 2017-01-30 criteria provided, single submitter clinical testing

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