England captain Owen Farrell looks set to miss the Six Nations opener against Scotland after Saracens confirmed he suffered an injury in training.
Head coach Eddie Jones named his 36-man squad for the Six Nations on 18th January with six uncapped players getting the nod, while Farrell, who hasn't played since November, was also in the party.
The Saracens ace picked up an ankle injury in the 32-15 Autumn International victory over Australia at Twickenham on 13th November.
Farrell was forced to miss the 27-26 win over world champions South Africa seven days later but he was on the road to recovery after returning to training for Saracens.
It appeared that the fly-half was set to feature in Saturday's Challenge Cup meeting encounter with London Irish, however, his club confirmed that will no longer happen.
Saracens said in a statement: "Owen Farrell suffered an injury in training this week ahead of the game against London Irish, ruling him out of the match.
"Owen was back in full training having recovered from the ankle injury he sustained against Australia during the Autumn internationals.
The 2022 edition of the Six Nations is scheduled to get underway on 5th February when England, who are priced at 5/2 to win the competition, head to Murrayfield to face Scotland.
Scotland, priced at 2/1 to prevail on home soil, lifted the Calcutta Cup in 2021 courtesy of an 11-6 win at Twickenham, and England can be backed at 2/5 to earn some revenge north of the border.
Jones was hoping to have Farrell available but Saracens say the number 10 will visit "a specialist early next week", and he isn't expected to join the rest of his teammates at their training camp in Brighton.
A squad update is set to be announced by Jones, who is seeking to improve on England's dismal fifth-place finish in the 2021 Six Nations, and a new captain is likely to be announced.
The leading contender appears to be Northampton Saints forward Courtney Lawes, who has previous experience of leading the national side.
Lawes captained the Red Rose for the first time on 6th November 2021 in a routine 69-3 over Tonga at HQ, while he was also skipper when they defeat the Springboks later that month.
The 32-year-old received high praise for his performance that day and should be duly rewarded with another opportunity for a key clash in Edinburgh.
Saracens' statement also leaves Jones with a decision to make with regards to who will start at fly-half and Marcus Smith could well be the man to step in.
The Harlequins playmaker is still relatively green, having made his senior debut in July 2021 and he boasts just four caps, however, he also impressed during the November Tests.
Smith's accuracy with the boot was essential in guiding England to victory over South Africa, with his 79th-minute penalty edging the hosts one point clear.
Having already proved his worth against formidable opposition, Jones should have no hesitation in turning to the 22-year-old.
Manu Tuilagi and Henry Slade started at 12 and 13 respectively in England's most recent outing and the latter should retain his spot.
Tuilagi is not in the squad as he continues to work his way back from a hamstring issue so Joe Marchant or Mark Atkinson could come into contention.