Scotland coach Gregor Townsend has named Finn Russell in his team to face England after the fly-half missed the Autumn Nations Cup through injury.
Full-back Stuart Hogg will lead the side with Cameron Redpath making his debut for the national side.
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"We learned a lot about ourselves and where the game is going during our Autumn campaign, and we aim to build on this base during the next seven weeks," Towsend said in a statement.
"It's always a pleasure to welcome a new player into our squad and we are looking forward to Cam Redpath winning his first cap on Saturday. We have been really impressed with Cam's contributions in the time he has been with us in camp.
"There are a number of experienced players in the backline to help make his transition to Test rugby go as smoothly as possible, and he has the mindset and skillset to thrive at this level."
Wingers Sean Maitland and Duhan van der Merwe are part of five changes to the side that faced Wales in the postponed Six Nations in October.
Matt Ferguson starts at No. 8 while another debut is handed to hooker George Turner.
Here is your @Scotlandteam to face @EnglandRugby at Twickenham on Saturday in the opening round of @SixNationsRugby, live on @ITV 🏴#AsOne
— Scottish Rugby (@Scotlandteam) February 4, 2021
Rory Sutherland and Zander Ferguson make up the front-row with Turner.
Ali Price partners Russell and Chris Harris is paired with Redpath.
Scott Cummings and Jonny Gray feature at second row, with Hamish Watson and Jamie Ritchie completing the pack.
The Calcutta Cup game marks 150 years since the two sides first met and Scotland will commemorate the occasion with a name from the 1871 team embroidered on each jersey.
Scotland team
Stuart Hogg (captain), Sean Maitland, Chris Harris, Cameron Redpath, Duhan van der Merwe, Finn Russell, Ali Price, Rory Sutherland, George Turner, Zander Fagerson, Scott Cummings, Jonny Gray, Jamie Ritchie, Hamish Watson, Matt Fagerson.
Replacements: David Cherry, Oli Kebble, WP Nel, Richie Gray, Gary Graham, Scott Steele, Jaco van der Walt, Huw Jones.