Submissions for variant NM_001048174.2(MUTYH):c.1393-51_*2del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358085	SCV001553734	pathogenic	Familial adenomatous polyposis 2		no assertion criteria provided	clinical testing	The MUTYH c.349-?_1650+?del variant (chr:1 g.45794978_45798996del GRCh37) results in the deletion of exons 4-16. The precise breakpoints of this deletion were not determined nor were the effects of this variant on the resulting mRNA or protein product determined, however this deletion includes the end of the open reading frame of MUTYH and is predicted to result in a truncated or absent protein and loss of function. Biallelic loss of function variants in the MUTYH gene are an established mechanism of disease in MUTYH-associated polyposis. In addition, this variant was identified in the literature in the homozygous state in a patient with clinically suspected MUTYH-associated polyposis (Torrezan 2011). The variant was not identified in dbSNP, ClinVar, or UMD-LSDB nor was it identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.