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The response of the East Antarctic Ice Sheet to global warming represents a major source of uncertainty in sea-level projections. Thinning of the East Antarctic George V and Sabrina Coast ice cover is currently taking place, and regional ice-sheet instability episodes might have been triggered in past warm climates. However, the magnitude of ice retreat in the past cannot yet be quantitatively derived from paleo-proxy records alone. We propose that a runaway retreat of the George V coast grounding line and subsequent instability of the Wilkes Basin ice sheet would either leave a clear imprint on the water isotope composition in the Talos Dome region or prohibit a Talos Dome ice-core record from the Last Interglacial altogether. Testing this hypothesis, our ice-sheet model simulations suggest that Wilkes Basin ice-sheet retreat remained relatively limited during the Last Interglacial and provide a constraint on Last Interglacial East Antarctic grounding line stability.