ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.55C>T (p.Arg19Ter) (rs587780088)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115767 SCV000149676 pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing This pathogenic variant is denoted MUTYH c.55C>T at the cDNA level and p.Arg19Ter (R19X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the homozygous or compound heterozygous state in at least two individuals with polyposis and/or colorectal cancer (CRC) and was observed in the single heterozygous state in other individuals with CRC and/or polyps (Jones 2009, Nielsen 2009, Vogt 2009, Kuno 2012, Shinmura 2014, Li 2017, Takao 2018). We consider MUTYH Arg19Ter to be pathogenic.
Invitae RCV000206117 SCV000260463 pathogenic MYH-associated polyposis 2020-06-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg19*) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with adenomatous polyposis and colorectal cancer (PMID: 19394335, 22641385, 24799981). ClinVar contains an entry for this variant (Variation ID: 127845). Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV000447652 SCV000537664 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000447652 SCV000670153 pathogenic Hereditary cancer-predisposing syndrome 2020-09-28 criteria provided, single submitter clinical testing The p.R19* pathogenic mutation (also known as c.55C>T), located in coding exon 2 of the MUTYH gene, results from a C to T substitution at nucleotide position 55. This changes the amino acid from an arginine to a stop codon within coding exon 2. The predicted stop codon occurs within the first 150 nucleotides of the MUTYH gene. This alteration may escape nonsense-mediated mRNA decay and/or be rescued by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat. Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci. Rep. 2017 May 10;7(1):1653). However, the impacted region is critical for protein function (Ambry internal data). This mutation has been reported in individuals with clinical diagnoses of MUTYH-associated polyposis, including one male diagnosed with colon cancer at age 43 who had 60-70 total colon polyps and co-occurrence with MUTYH c.1147delC (Nielsen M et al. Gastroenterology. 2009 Feb;136:471-6; Jones N et al. Gastroenterology. 2009 Aug;137:489-94; Vogt S et al. Gastroenterology. 2009 Dec;137:1976-85; Li CG et al. J. Gastroenterol. Hepatol. 2017 Oct;32(10):1723-1729). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics,Fulgent Genetics RCV000763343 SCV000894025 pathogenic MYH-associated polyposis; Pilomatrixoma; Neoplasm of stomach 2018-10-31 criteria provided, single submitter clinical testing
Pathway Genomics RCV000144639 SCV000189966 pathogenic Carcinoma of colon 2014-07-24 no assertion criteria provided clinical testing

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