The Latics are resigned to losing the Ecuador international and should recoup a fee of around £21m for the midfielder, with Manchester United also believed to be battling it out for his services.
Wigan boss Steve Bruce has openly admitted the 23-year-old will move on in the summer and Madrid have been long-term admirers after attempting to lure him to the Bernabeu last January.
Valencia's agent, Diego Herrera, revealed Real have now tabled an offer for the midfielder and that the Latics are awaiting other offers before allowing the player to leave.
"I believe Wigan will sell Antonio for the right offer and they will decide that once they receive that," Herrera told Skysports. "Real Madrid made an offer last week, but nobody from Wigan has told me of an offer from Manchester United.
"There are a number of interested clubs and I will speak with Wigan about it this week.
"Once the season is over I expect offers to be made and I will sit down with Antonio and decide what offer is in his best interests. We've not yet talked about which club he would prefer.
''Honestly I think it's really difficult that he remains at Wigan. I would anticipate that he leaves this summer.''We have to see what will happen in the next few weeks. We're not in any rush.