Every single year, the top teams in college basketball earn high seeds in the NCAA Tournament that should, in theory, insulate them from a shocking upset.

And every year, March Madness strikes.

We know by now that any team can lose at any moment – just ask Virginia – even if they seem invulnerable on paper.

And with this year’s field in particular, there are a handful of highly ranked teams that look ripe for an upset in the first few rounds.

Here are five top seeds on upset alert in this year’s NCAA Tournament, with their title odds courtesy of BetMGM:

The Cougars enter the NCAA Tournament as title favorites and have ranked No. 1 in KenPom’s adjusted efficiency margin just about the entire season.

But all of that could go up in smoke if Marcus Sasser (17.1 PPG) isn’t healthy.

Houston’s star senior, who scored 30 points in his last full game, sat out the AAC Tournament final with a non-contact groin injury that the team hasn’t shed any updates on.

The Cougars looked lost in that game without him, losing by 10 points to a Memphis team it had beaten twice in the regular season.

Now Houston could be staring down a future without Sasser, which doesn’t bode well for its chances to survive a tricky Midwest Region.

The Boilermakers have been the No. 1 ranked team in the country for much of the year, but there’s no doubt this team has a couple of fatal weaknesses come tournament time.

One is its inexperienced backcourt: freshman guards Braden Smith and Fletcher Loyer elevate this team to nearly unbeatable when their shots are falling, but they’re prone to cold stretches and have a nasty turnover streak at times – especially against aggressive press defenses.

Purdue also runs virtually everything through 7-4 center Zach Edey (22.3 PPG), whose 32.6% usage rate is the highest of any player in the 68-team field.

If he runs into foul trouble at any point, this team could be bracing for a quick exit in the East Region.

At full strength, Mick Cronin’s group would be one of the best bets to emerge from the West Region. But this team is anything but healthy.

A week ago, the Bruins lost Jaylen Clark – the team’s third-leading scorer (13 PPG) and one of the best defenders in all of college basketball – to a season-ending Achilles injury.

It’s hard to overstate the loss: UCLA’s defense ranks first in the country and allowed fewer than 85 points per 100 possessions when Clark was on the floor.

Then center Adem Bona, the Pac-12 Freshman of the Year, injured his shoulder a few days later and missed the team’s loss to Arizona in the Pac-12 Tournament Final.

He could be back for the tourney, but UCLA is a wounded giant either way with a complicated path ahead.

The Wildcats showed their elite upside this year with multiple wins over top-10 teams in a loaded Big-12. But they also have a lower floor than about any top seed in the tournament.

Kansas State posted a .500 record over its final 16 games and had a losing record (7-8) in games away from home, which included two straight losses to close the year.

The Wildcats also have a nasty turnover problem, giving it away on 21.3% of possessions since Feb. 1 – which ranked 340th out of 363 teams in that span.

Now they face a pesky Montana State team in the first round that excels at forcing turnovers and getting to the line, which is a key weakness of this Kansas State defense.

If the ‘Cats survive that, they’ll likely have a surging Kentucky waiting for them in the second round. Good luck.

This list wouldn’t be complete without Virginia, which brought us the biggest collapse by a No. 1 seed in NCAA Tournament history and is vulnerable to another early exit this year.

Among the 16 teams with a top-four seed, Virginia is ranked the lowest by adjusted efficiency margin (34th) and has by far the worst offensive rating (74th), which is especially concerning given how methodical Tony Bennett’s team are and how difficult it can be for them to erase a big deficit.

Consider that the Cavaliers’ defense, oft-vaunted in March, is just average at preventing threes, and the recipe is there for another mid-major to take this team down in the Cinderella-friendly South Region.

Furman isn’t perfectly built to take advantage, but Charleston could pose a threat in the second round if it gets past San Diego State – a team that plays Virginia’s style but better.