Alex Mitchell has been ruled out of England’s crucial Six Nations match against Scotland on Saturday with a knee injury, dealing Steve Borthwick a major setback as he plots his side’s first Calcutta Cup win in four years.

Mitchell will have further tests to determine whether he will miss the rest of the tournament but the scrum‑half’s absence from ­Murrayfield is a significant blow.

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The 26-year-old has started both of England’s matches in the championship so far this year after overcoming an infected wound to his leg to appear in their opener against Italy, scoring a crucial second-half try in Rome, before facing Wales at Twickenham. With Marcus Smith nursing a calf injury, the two half-backs Borthwick intended on starting at the beginning of the championship are sidelined.

In Mitchell’s absence, Danny Care is the favourite for the No 9 jersey against Scotland and in line for his 99th cap, having come off the bench against both Italy and Wales.

Ben Spencer has been acting as the third scrum-half in the squad and can now be hopeful of making a first appearance for England since the 2019 World Cup final and winning a fifth cap against Scotland, though Harry Randall has also been called up to a 36-man squad. The Bristol scrum‑half has just six caps to his name and was named last week in the England A squad preparing to face Portugal on 25 February but Ben Youngs’s retirement after the World Cup highlights England’s lack of depth at scrum-half.

Mitchell’s withdrawal comes after he sustained the injury during England’s training session at ­Twickenham, which was watched by 10,000 people, on Friday. He has been in fine form for Northampton this season, helping to guide the Saints to the top of the Premiership and into the knockout stages of the Champions Cup and he has been tasked with igniting England’s remodelled attack in the Six Nations.

Mitchell established himself as England’s first-choice scrum‑half during the World Cup and started all games aside from the pool‑stage win against Chile and the bronze‑medal victory against Argentina – matches for which he was rested. He was cut from a wider squad early in the summer but was the beneficiary of Jack van Poortvliet’s ankle injury and took full advantage of his reprieve.

In better news for Borthwick, as reported by the Guardian last week, Ollie Lawrence has been passed fit to join the squad after completing his rehab last week. The 24-year-old centre offers more ballast to England’s midfield and bolsters their options, ­joining Manu Tuilagi in being ­available ­having also missed the first two games with a hip injury. Smith again comes into camp to continue his rehab but England have not put a timeframe on his return.