rs34612342

badMag 9.0

This is a variant in the MUTYH gene that changes a tyrosine to an cysteine.

Key Literature Trait Associations

MUTYH-Associated Polyposis and Colorectal Cancer

The MUTYH Y179C variant (c.536A>G, p.Tyr179Cys) is one of the two most common pathogenic MUTYH variants in Northern Europeans. MUTYH is a base excision repair enzyme that corrects oxidative DNA damage. Homozygous carriers or compound heterozygotes (one Y179C plus one G396D) have up to 28-fold elevated colorectal cancer risk. Monoallelic carriers have a modest ~34% increase that remains controversial. All biallelic carriers should receive intensive surveillance starting at age 18–20.

Theodoratou E et al. “A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants.” British Journal of Cancer (2010)

Allele C

OR 10.80

p —

N 36,089

Meta-analysis

European

Varela I et al. “Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.” Nature 469(7331):539-542 (2011)

Allele C

OR 1.34

p 5.0e-3

Meta-analysis

Tenesa A et al. “Association of MUTYH and colorectal cancer.” British Journal of Cancer (2006)

Allele C

OR —

p —

N 1,773

Preliminary work

European

Nielsen M et al. “Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis.” Gastroenterology (2009)

Allele C

OR —

p 1.0e-3

N 257

Candidate gene study

European

Extracolonic cancer risk in MUTYH-associated polyposis

Biallelic MUTYH mutation carriers, including those with Y179C, face substantially elevated risks for extracolonic malignancies beyond colorectal cancer. A study of 276 MAP patients found standardized incidence ratios of 129 for duodenal cancer, 7.2 for bladder cancer, and 5.7 for ovarian cancer compared to the general population. Overall extraintestinal malignancy risk was nearly doubled (SIR ~1.9). These extracolonic risks apply to confirmed MAP (biallelic) carriers and inform surveillance guidelines beyond colonoscopy.

Vogt S et al. “Expanded extracolonic tumor spectrum in MUTYH-associated polyposis.” Gastroenterology (2009)

Allele C

OR —

p —

N 276

Candidate gene study

European

Sutcliffe EG et al. “Multi-gene panel testing confirms phenotypic variability in MUTYH-Associated Polyposis.” Familial Cancer (2019)

Allele C

OR —

p —

N 82

Candidate gene study

multi-ancestry

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ClinVar annotation

Pathogenic★★★☆

68 submitters95 publications

Familial adenomatous polyposis 2; Endometrial carcinoma; not provided; Hereditary cancer-predisposing syndrome; not specified; Carcinoma of colon; Gastric cancer; Familial adenomatous polyposis 2;Gastric cancer; MUTYH-related disorder; Inherited polyposis and early onset colorectal cancer - germline testing; Dysembryoplastic neuroepithelial tumor; Medulloblastoma; Colorectal cancer; Pilocytic astrocytoma

rs34612342

Key Literature Trait Associations

MUTYH-Associated Polyposis and Colorectal Cancer

Extracolonic cancer risk in MUTYH-associated polyposis

ClinVar annotation

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