Manu Tuilagi is expected to be left out of Steve Borthwick's England team to face Scotland at Twickenham on Saturday, with Joe Marchant in line to start in the centre.
Since his debut in 2011, Tuilagi, 31, has been a regular under successive England coaches when fit and available.
Despite being retained in the 29-man squad on Tuesday, it is understood the Sale powerhouse is set to miss out.
The England team will be confirmed at 14:45 GMT on Thursday.
Injuries to Henry Slade, Elliot Daly and Dan Kelly have reduced Borthwick's options in the midfield, with Marcus Smith and Owen Farrell likely to again combine at fly-half and inside-centre.
Marchant's inclusion will provide England with pace and dynamism, as well as a club understanding with Harlequins team-mate Smith, but without the raw power of Tuilagi.
Elsewhere, London Irish's Ollie Hassell-Collins is expected to make his debut, with Max Malins returning to the back three.
Vice-captain Ellis Genge has hailed the impact of the new regime, with Borthwick replacing Eddie Jones in December.
"I think Eddie Jones is a world-class coach, obviously," Genge told BBC Sport.
"But when a new coach comes into any environment you have a bit more of a bounce and excitement, because it is the unknown.
"We've had a reaction across the whole board - it's been quite infectious - of being really excited.
"It is just the magic of having a new person steering the wheel.
"I'm not going to pick apart what we have done prior to this. I just genuinely have a real big excitement. It is very clear where we want to go."
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