Open AccessNovel variant of unknown significance in MUTYH in a patient with MUTYH-associated polyposis: a case to reclassify
Author(s) -
Trilokesh D. Kidambi,
Dena Goldberg,
Robert L. Nussbaum,
Amie Blanco,
Sarah E. Umetsu,
Jonathan P. Terdiman,
Jeffrey K. Lee
Publication year - 2018
Publication title -
clinical journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.414
H-Index - 17
eISSN - 1865-7257
pISSN - 1865-7265
DOI - 10.1007/s12328-018-0870-4
Subject(s) - mutyh , surgical oncology , medicine , colorectal cancer , hepatology , phenotype , exon , clinical significance , germline , familial adenomatous polyposis , genetic testing , germline mutation , cancer , gene , genetics , mutation , biology
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.