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  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Sterling...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Sterling Shepard (87) celebrates his touchdown against San Francisco 49ers' D.J. Reed Jr. (32) late in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Odell...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Odell Beckham Jr. (13) makes a touchdown catch against San Francisco 49ers' Ahkello Witherspoon (23) in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • Curtis Riley leaps for a ball near the back of...

    Curtis Riley leaps for a ball near the back of the end zone against the 49ers in 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Odell...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Odell Beckham Jr. (13) can't make a catch in the end zone against San Francisco 49ers' Jimmie Ward (20) in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon Barkley (26) runs against the San Francisco 49ers in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Robbie...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Robbie Gould (9) celebrates his field goal against the New York Giants in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Antone...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Antone Exum Jr. (38) breaks-up a pass intended for New York Giants' Evan Engram (88) in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Alfred...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Alfred Morris (46) runs against the New York Giants in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Kyle...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Kyle Juszczyk (44) is tackled by New York Giants' Lorenzo Carter (59) in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon Barkley (26) runs against San Francisco 49ers' Richard Sherman (25) late in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: A San Francisco 49ers...

    SANTA CLARA, CA - NOVEMBER 12: A San Francisco 49ers fan adjusts his mask during the 49ers game against the New York Giants in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: A San Francisco 49ers...

    SANTA CLARA, CA - NOVEMBER 12: A San Francisco 49ers fan wears a mask during the 49ers game against the New York Giants in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. Few fans wore masks. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers starting...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers starting quarterback Nick Mullens (4) looks to throw against the New York Giants in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers head...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers head coach Kyle Shanahan yells at a referee during their game against the New York Giants late in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers head...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers head coach Kyle Shanahan talks to a referee during their game against the New York Giants late in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers starting...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers starting quarterback Nick Mullens (4) celebrates a touchdown with San Francisco 49ers' Mike Person (68) against the New York Giants in the third quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • San Francisco 49ers' DeForest Buckner (99) and San Francisco 49ers'...

    San Francisco 49ers' DeForest Buckner (99) and San Francisco 49ers' Dekoda Watson (97) sack New York Giants starting quarterback Eli Manning (10) in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' DeForest...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' DeForest Buckner (99) and San Francisco 49ers' Dekoda Watson (97) sack New York Giants starting quarterback Eli Manning (10) in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: Dekoda Watson (97) celebrates...

    SANTA CLARA, CA - NOVEMBER 12: Dekoda Watson (97) celebrates his sack on New York Giants starting quarterback Eli Manning (10) in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt Breida (22) runs against New York Giants' Landon Collins (21) in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon Barkley (26) runs with the ball against the San Francisco 49ers late in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' DeForest...

    (Nhat V. Meyer/Bay Area News Group)

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' DeForest Buckner (99) and Fred Warner (48) react after the New York Giants scored a touchdown late in the fourth quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' K'Waun...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' K'Waun Williams (24) and San Francisco 49ers' Fred Warner (48) tackle New York Giants' Sterling Shepard (87) in the first quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Robbie...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Robbie Gould (9) celebrates his field goal with San Francisco 49ers' Joe Staley (74) against the New York Giants in the first quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers starting...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers starting quarterback Nick Mullens (4) throws against the New York Giants in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt Breida (22) scores a touchdown against New York Giants' B.J. Goodson (93) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Robbie...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Robbie Gould (9) kicks a field goal against the New York Giants late in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants' Saquon Barkley (26) runs against San Francisco 49ers' Jimmie Ward (20) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: New York Giants starting...

    SANTA CLARA, CA - NOVEMBER 12: New York Giants starting quarterback Eli Manning (10) throws against the San Francisco 49ers in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt Breida (22) scores a touchdown against New York Giants' B.J. Goodson (93) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Dekoda...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Dekoda Watson (97) high-fives Spencer Kiefer (1), from the Paradise High School football team, before the San Francisco 49ers game against the New York Giants at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt Breida (22) scores a touchdown against New York Giants' B.J. Goodson (93) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' George...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' George Kittle (85) is tackled after a catch against New York Giants' Lorenzo Carter (59) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Matt Breida (22) can't make a catch against New York Giants' Lorenzo Carter (59) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Richard...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Richard Sherman (25) tackles against New York Giants' Saquon Barkley (26) in the second quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Sheldon...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Sheldon Day (96) and San Francisco 49ers' K'Waun Williams (24) dive for a loose ball against New York Giants' Spencer Pulley (77) in the first quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. Pulley recovered the ball. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Sheldon...

    SANTA CLARA, CA - NOVEMBER 12: San Francisco 49ers' Sheldon Day (96) and San Francisco 49ers' K'Waun Williams (24) dive for a loose ball against New York Giants' Spencer Pulley (77) in the first quarter at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. Pulley recovered the ball. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: The Paradise High School...

    SANTA CLARA, CA - NOVEMBER 12: The Paradise High School football team lines up with the San Francisco 49ers for the National Anthem before the 49ers game against the New York Giants at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

  • SANTA CLARA, CA - NOVEMBER 12: The Paradise High School...

    SANTA CLARA, CA - NOVEMBER 12: The Paradise High School football team lines up with the San Francisco 49ers for the National Anthem before the 49ers game against the New York Giants at Levi's Stadium in Santa Clara, Calif., on Monday, Nov. 12, 2018. (Nhat V. Meyer/Bay Area News Group)

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Cam Inman, 49ers beat and NFL reporter, San Jose Mercury News, for his Wordpress profile. (Michael Malone/Bay Area News Group)
PUBLISHED: | UPDATED:

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SANTA CLARA — Nick Mullens was all set to win his encore as the 49ers starting quarterback. But, as was the case in the pre-Mullens era, the 49ers defense couldn’t hold a late lead.

Eli Manning threw a 3-yard touchdown pass to Sterling Shepard with 53 seconds remaining to hand the 49ers a 27-23 defeat.

“I’m extremely disappointed,” coach Kyle Shanahan said. “We put ourselves in position where we should have won that game. We had a chance to step on their throat and didn’t. We didn’t make plays at the end.”

In the end, the 49ers (2-8) lost by blowing a fourth-quarter lead for the fourth time this season, doing so earlier in road games at the Arizona Cardinals (15-3 lead), the Green Bay Packers (30-23 lead) and the Los Angeles Chargers (27-26).

“I can’t tell you how many times we lost by two or three points when we should have won this year, and we’ve got to finish,” said running back Matt Breida, who ran for 101 yards and a touchdown and added 31 receiving yards and a touchdown.

The 49ers head into the bye and return to action Nov. 25 at the Tampa Bay Buccaneers (3-6). The Giants (2-7) snapped a five-game losing streak.

“We had multiple opportunities to end it and didn’t, so it’s obviously something we have to figure out, because it’s happened multiple times this season,” tight end George Kittle said. “If we don’t figure it out, it’s not going to be a fun season. We can figure it out because I love all the guys in the locker room and great coaches. I love playing for coach Shanahan. We’re going to fix this and we have the right guys to do so.”

Mullens and the 49ers weren’t finished off until the final play, as after he led them to the Giants’ 21-yard line, he took one last snap with one second remaining and rifled a desperation pass out of the back of the end zone. He hoped a personal-foul penalty would be called on the Giants. His hopes were dashed, as was his immortal status in 49ers lore.

“It’s hard to evaluate the overall performance,” Mullens said. “There are so many plays that are running through my head where it’s very frustrating. I mean everybody did a great job.

“Shoot, when you’re out on the field, you really sense the brotherhood. Everybody battled their butts off. But effort doesn’t always win games. Execution does. That’s why I’m pretty frustrated with myself.”

Mullens, who threw three touchdown passes and no interceptions in his triumphant debut over the Raiders, finished 27-of-39 for 250 yards with a touchdown pass and two interceptions.

Manning, the two-time Super Bowl MVP who hadn’t been promised another start beyond this one, responded with a three-touchdown effort (19-of-31, 188 yards, no interceptions).

“Eli is really good at engineering those come-from-behind drives,” Giants coach Pat Shurmur said. “That was terrific. He hung in there, made some really good throws and got us in the end zone. That’s the mark of a quarterback.”

The 49ers too often settled for field goals, and they took a 23-20 lead on Robbie Gould’s third field goal of the night, a 30-yard kick that capped a six-minute drive that left only 2:46 for the Giants.

But that was enough time for the 15th-year veteran Manning, whose job was under familiar scrutiny. Needing a big play on second-and-20, Manning went after the 49ers cornerback who’s been picked on all season: Ahkello Witherspoon. Officials flagged Witherspoon for pass interference as he covered Odell Beckham Jr., who caught a third-quarter touchdown pass against Witherspoon with blown coverage help by the safety.

KEY IMPRESSIONS

OUTSIDE THROWS: Mullens’ first career interception enhanced a concern: his arm strength to fire passes toward the sideline boundary, especially in the flat.

After a play-action fake, Mullens waited at the goal line, then threw wide left toward Kendrick Bourne, who prevented Janoris Jenkins from intercepting it for a potential pick-six, and the ball deflected to linebacker B.J. Goodson at the 49ers’ 12-yard line. The Giants’ first touchdown came two snaps later, Manning to Beckham on a 10-yard strike.

Said Mullens: “It wasn’t necessarily a terrible read. But it was late. And the cornerback made a good play on it.”

Mullens responded to his first career interception with a 75-yard touchdown drive. He completed all three passes on that series — including 18- and 22-yarders to George Kittle — to set up Matt Breida’s 3-yard touchdown run.

In the second quarter, Mullens completed a pass on  the left sideline to George Kittle, but only after safety Landon Collins went for and just missed a potential pick-six. Just before halftime, another Mullens pass outside the numbers nearly resulted in an interception inside the 5, as it was thrown behind Dante Pettis.

Goodson also had the Giants’ second interception of Mullens, and that one also came on a tipped pass, thrown behind and off the hands of Marquise Goodwin. “Bad ball placement and bad luck,” Mullens said.

Mullens said he’s “not worried” about if he’ll remain the starter and is simply frustrated about his first loss.

Kittle (nine catches, 83 yards) vouched for him: “Nick’s a stud. He was great. He’s a great voice (in the huddle). I love playing with him. He’s done everything we’ve asked of him and more. He’s going to keep doing that and keep slinging it.”

ANGRY WITHERSPOON: Witherspoon committed what Richard Sherman called a “cardinal sin of football” by expression his frustration by calling out a teammate, which in this case was whichever 49ers safety (Antone Exum or Jimmie Ward) that was supposed to help him defend Beckham on what was a 20-yard touchdown catch on third-and-7, cutting the 49ers lead to 20-17.

Witherspoon raised his arms in frustration. Shanahan did not approve of that gesture in his postgame presser, saying: “Man up. Don’t put that on tape. We’ll deal with it when we come in.”

Asked if he expected safety help as Shanahan and Sherman suggested, Witherspoon would only say: “I was expecting the ball not to be completed” On if he disagreed with the last-series, pass-interference call: “I did. But I also disagree with me not turning my head because I would have had INT. Once again, self-inflicted wounds”

BREIDA OR BARKLEY: While Barkley enhanced his rookie-of-the-year bid with a bevy of solid runs, it was his 49ers counterpart, Matt Breida, who produced more yards and points. Still, Barkley won.

Breida’s first-half rushing touchdown and third-quarter touchdown reception showed how capable he’s been as a dual threat that’s needed in Shanahan’s offense. He ran for over 100 yards for the first time since a Week 2 win over the Lions, despite coming in and out of the game with an aggravated ankle injury.

Breida finished with 17 carries for 101 yards and three catches for 31 yards.

Barkley, meanwhile, a reliable threat, and anytime the 49ers made a clean tackle on him, it seemed like a remarkable feat, including a few tackles by cornerback Richard Sherman. Barkley finished with 20 carries for 67 yards, and four receptions for 33 yards.

NOTES

— As a result of the Butte County fire that’s burned since Friday, the air-quality index at kickoff was 156, which registered as “unhealthy” but it didn’t reach the 200 mark that could have resulted in the game’s postponement.

— Running back Matt Dayes got promoted over Jeff Wilson Jr. from the 49ers practice squad Monday. Dayes, a Cleveland Browns backup last season, helped fill the void of third running back Raheem Mostert, who broke his arm last game.

— Safety Tyvis Powell, who started last game against the Raiders, got released. Antone Exum started at strong safety as Jaquiski Tartt (shoulder) missed his second straight game.

— Also inactive for the 49ers: Wide receiver Pierre Garçon (knee), linebacker Reuben Foster (hamstring), quarterback Tom Savage, defensive end Jullian Taylor and offensive linemen Erik Magnuson and Shone Coleman.

— Paradise High School’s football team, which forfeited its playoff opener last weekend after the devastating Camp Fire, got bused by the 49ers to the game and was on the sidelines for the national anthem.