ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1171C>T (p.Gln391Ter) (rs587783057)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569738 SCV000670131 pathogenic Hereditary cancer-predisposing syndrome 2015-10-09 criteria provided, single submitter clinical testing
Color RCV000569738 SCV000685548 pathogenic Hereditary cancer-predisposing syndrome 2016-11-28 criteria provided, single submitter clinical testing
Counsyl RCV000410310 SCV000487361 pathogenic MYH-associated polyposis 2016-06-08 criteria provided, single submitter clinical testing
GeneDx RCV000413062 SCV000490628 pathogenic not provided 2018-08-06 criteria provided, single submitter clinical testing This variant is denoted MUTYH c.1171C>T at the cDNA level and p.Gln391Ter (Q391X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as MUTYH Gln377Ter using an alternate reference sequence (NM_001048171.1), has been reported in the homozygous or compound heterozygous state in several individuals with multiple adenomatous polyps and/or colorectal cancer (Nielsen 2005, Aretz 2006, Croitoru 2007, Cleary 2009), and functional studies by Ali et. al. (2008) demonstrated severely defective glycosylase and DNA binding activities. Based on currently available evidence, we consider MUTYH Gln391Ter to be pathogenic.
Invitae RCV000410310 SCV000545766 pathogenic MYH-associated polyposis 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 391 (p.Gln391*) of the MUTYH gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587783057, ExAC 0.002%). This variant has been reported in individuals affected with MUTYH-associated polyposis in the homozygous state or in combination with another pathogenic variant (PMID: 16140997, 19732775, 24444654). This variant is also known as c.1129C>T (p.Q377X) in the literature. ClinVar contains an entry for this variant (Variation ID: 156509). An experimental study has shown that this missense change disrupts MUTYH protein function and results in reduced glycosylase activity and DNA binding activity. (PMID: 18534194). Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000410310 SCV000837752 pathogenic MYH-associated polyposis 2018-07-02 criteria provided, single submitter clinical testing
Pathway Genomics RCV000144635 SCV000189962 pathogenic Carcinoma of colon 2014-07-24 no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000413062 SCV000888297 pathogenic not provided 2017-11-24 criteria provided, single submitter clinical testing

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