If you are manually assigning a username to a user's record and after entering the new username, you're unable to save, the most common cause is that the user name you are adding is already in use. Try entering a different, unique username and see if this saves. If so, this confirms the username you were attempting to add is being used by another user in the system. 

You can create a list of usernames, and filter for the specific username you're trying to add, to see which user already has this username assigned.

Click here for steps on how to create a list of usernames.