343 Background: MYH-associated polyposis is an autosomal recessive syndrome caused by biallelic mutations in the base excision repair gene MYH. Initial reports indicated that a majority of European biallelic individuals carried two founder mutations, Y165C and G382D. A common MYH analysis strategy involves evaluation of the two founder mutations (FMs) with subsequent full sequencing only if one of the FMs is identified. This study aimed to determine the sensitivity of full MYH sequencing over the strategy described above in a cohort of individuals that has undergone genetic testing by a commercial laboratory. Methods: A retrospective analysis was performed on 1,522 individuals who had clinical MYH testing ordered either independently or in conjunction with APC gene analysis. All patients underwent MYH analysis for Y165C and G382D. Subsequent full gene sequencing was performed for all patients, except for those biallellic for the two FMs. Demographic, personal, and family cancer histories were collected on the test request form. Results: 86 biallelic individuals were identified, with 47 carrying two FMs, 18 carrying one FM and one mutation identified on sequencing, and 21 carrying biallelic mutations identified only on full sequencing. 21/86 (24.4%) biallelic MYH mutation carriers would have been missed by FM analysis only. The mutation spectrum is distributed among different ethnicities (Table). The majority of individuals met clinical criteria for a polyposis syndrome, with 21 individuals reporting more than 99 adenomas (24.4%) and 50 individuals reporting 20-99 adenomas (58.1%). Conclusions: Analysis of only the two MYH FMs would miss 24% of biallelic individuals in our cohort. Due to the ethnicity distribution of mutations, it is difficult to predict who would be missed by this strategy. Consideration of MYH full sequencing is warranted to achieve highest clinical sensitivity. [Table: see text]