Clinical Journal of Gastroenterology

, Volume 11, Issue 6, pp 457–460 | Cite as

Novel variant of unknown significance in MUTYH in a patient with MUTYH-associated polyposis: a case to reclassify

  • Trilokesh D. KidambiEmail author
  • Dena Goldberg
  • Robert Nussbaum
  • Amie Blanco
  • Sarah E. Umetsu
  • Jonathan P. Terdiman
  • Jeffrey K. Lee
Case Report


MUTYH-associated polyposis (MAP) is a hereditary cancer syndrome that is caused by biallelic pathogenic variants in the MUTYH gene and should be evaluated for in patients with an attenuated colonic polyposis phenotype. Monoallelic pathogenic variants in MUTYH are associated with a moderate increased risk of colorectal cancer but not with the polyposis phenotype. We present a case of a patient presenting with multiple colonic adenomatous polyps, whose germline testing revealed a heterozygous pathogenic variant in MUTYH in exon 13, c.1187G > A (p.Gly396Asp) as well as a heterozygous variant of unknown significance (VUS) in MUTYH in exon 14, c.1379T > C (p.Leu460Ser). We interpret the VUS as pathogenic in light of the patient’s phenotype; the fact that the VUS was in trans with a known pathogenic variant; and because all the in silico predictors suggested, it was likely to be deleterious. This case highlights the importance of a gastroenterologist recognizing the indication for genetic testing in a patient with greater than ten adenomas, the importance of a genetic counselor in interpretation of results, and is the first report of the specific variant in the literature with clinical information to suggest that it is likely pathogenic.


MUTYH MYH-associated polyposis Hereditary cancer syndrome Polyposis Multiple colorectal adenomas 



National Cancer Institute (K07CA212057) and American Gastroenterological Association grant both awarded to JKL.

Compliance with ethical standards

Conflict of interest

Trilokesh Kidambi, Dena Goldberg, Jonathan Terdiman, Sarah Umetsu and Jeffrey Lee declare they have no conflict of interest. Robert Nussbaum is the chief medical officer at Invitae Corp. Amie Blanco’s spouse is a paid employee of Genentech.

Human/animal rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Supplementary material

12328_2018_870_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 KB)


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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  1. 1.Division of GastroenterologyUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Hereditary GI Cancer Prevention Program, Helen Diller Family Comprehensive Cancer CenterUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Invitae CorporationSan FranciscoUSA
  4. 4.Department of PathologyUniversity of California, San FranciscoSan FranciscoUSA
  5. 5.Department of GastroenterologyKaiser Permanente Northern CaliforniaSan FranciscoUSA

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