Griffin guided the club to the finals in 2016 and 2017 and leaves the fifth-placed Panthers on track for another finals appearance in 2018.

There had been much speculation about Griffin’s relationship with Panthers general manager Phil Goudl, and the playing group.

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"After discussions with Anthony Griffin it is time to end that speculation,” Panthers Group CEO Brian Fletcher said in a statement on Monday.

“By mutual agreement, the club and Anthony have agreed to part ways, effective immediately.”

West Tigers coach Ivan Cleary has emerged as the Panthers' No.1 target to replace Griffin, despite having two years left to run on his NRL contract.

It's understood the former Panthers coach has spoken to Penrith officials in the last few weeks.

Only last week he reiterated his desire to work with his son, Panthers half-back Nathan Cleary, at some point during his career.

But the Wests Tigers have issued a hands-off edict to Penrith as the Panthers attempt to lure the senior Cleary back to the foot of the mountains.

Tigers CEO Justin Pascoe told AAP he would not consider granting Cleary an early release with the highly respected coach in the second year of his three-and-a-half year deal.

"No mate we would not," Pascoe said when asked if they would consider letting Cleary go.

Nathan is off contract at the end of 2019 and under NRL rules will be able to negotiate with rival clubs from November 1.

The Blues State of Origin No.7 said he will consider his next career move on his 21st birthday in mid-November.

Should the Panthers snag Cleary, it would virtually ensure Nathan, considered a once-in-a-generation talent, would remain at the Panthers.

There are several sticking points, in particular the Tigers' willingness to let him go and Cleary's relationship with the Panthers after he was sacked less than three years ago.

Panthers general manager Phil Gould denied his relationship with Cleary had soured after he was axed following the 2015 season.

"It's good," Gould said.

"I don't see him all that often but I've got no problem with Ivan.

"I've known him for 25 years. The Ivan decision was made in his best interests and my best interests.

"I believe I was right at the time – whether or not I was, it doesn't matter."