With the game seemingly headed for a shootout, Frattin corralled a bouncing puck while skating down the left side and flipped the puck over the shoulder of the Sabres goalie Ryan Miller and into the right side of net for the game-winner.
Frattin also scored in the second period while Cody Franson added a goal and an assist for Toronto, which broke a two-game skid.
Jason Pominville, Andrej Sekera and Mikhail Grigorenko scored for Buffalo, which fell for the fourth straight time.
Miller finished with 20 saves.
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