"I don't think we've ruled [Garoppolo] out, but I can on you guys' radio show, I guess," Shanahan said. "Jimmy's not going to be playing, so Nick's going to be good to go. He's got all the reps this week, and he's fired up."
Starter Jimmy Garoppolo has not practiced this week and isn't expected to do so on Friday as he continues to recover from a high-ankle sprain suffered this past weekend against the New York Jets.
Shanahan said the offense wouldn't change for Mullens. It will just be a different guy running his offense.
"Nick's a machine," Shanahan continued. "He prepares as hard as anyone I've ever been around. He knows the offense inside and out. When he's given reps in practice, specific reps like he's gotten all this week, he's very crisp and prepared for every moment that he has.
"We've got two good backups in both Nick and C.J. (Beathard). They both do a hell of a job in practice every day. It would be very tough for me to decide between the two of them in practice, but the last time they played, Nick played so well when he got his chance. That's why we never went back. ... I expect him to play very good this week."
Shanahan added that Garoppolo won't be suited up on Sunday and probably won't even be on the sideline with his teammates.
Shanahan also confirmed that neither Raheem Mostert nor Tevin Coleman will play on Sunday, which means it will be Jerick McKinnon getting the start with Jeff Wilson, Jr. backing him up at running back.
"Jet McKinnon, he's done a great job these last two weeks," Shanahan said. "I'm real happy for him to be in this spot that he's been through to where he's got an opportunity to get a lot more opportunities this week."
The coach also confirmed that the 49ers would promote JaMycal Hasty from the practice squad by Saturday.
Tight end George Kittle will be a game-time decision. Shanahan said if Kittle or his doctors aren't 100 percent confident in his health, the tight end will not play.
Update: The 49ers later ruled Kittle out for Sunday's game against the Giants.
"Today will be a big day," Shanahan noted. "It's gotten better each day. We haven't gotten out there yet for our Friday practice, so we'll go out there today, test him a little bit more, and I'll talk to him after, talk to the doctors after. Then we'll make a decision.
"But I can promise you, if there's any hesitation at all in George, which there rarely is, but if there is at all, and if there's any hesitation by the doctor at all, he won't be out there.
"If all of them are extremely confident that he can go out there and protect himself and be 100 percent, then I think the decision is already made for me."
You can listen to the entire conversation with Shanahan below.
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