What are some notable blunders in history that resulted in huge loss?

Once the campaigns were underway, yes. But the opportunity came from a huge blunder by David Cameron. He called the referendum expecting an easy win for the remain side that would silence the anti-EU faction in his party and shore up his position as PM. Instead, the anti-EU faction won, prompting his own resignation and causing damage to the UK's economy, a loss of global influence, the loss of British people's right to live and work in the EU, and reopening difficult issues in Northern Ireland that had been laid to rest for years. It also arguably sped up the Conservative Party's lurch to the right and its embrace of UKIP-like policies, disempowering Conservative moderates and leading to the spiral of ever less competent governments we have seen since then. In particular, Boris Johnson's rise was a direct result of post-referendum power games among Conservative politicians.