I once wrote a program that calculated the inflight C of G of a large helicopter that was drawn from the C of G shift graph produced by the manufacturer. (Early 90's) As discussed here the C of G was purely an estimation as the graphs were produced by calculating the C of G shift during the consumption of fuel and from what tank.
As stated above this is an estimation. In flight in a large airliner I can see thousands of other variables creeping in. Distribution of passengers, use of potable water, use of inflight catering, movement of personnel throughout the flight and the position of the Captain's wallet
. Therefore even an aerodynamic calculation would be a 'snapshot' of the weight distribution of the aircraft at that time.
Good luck!
(Forgot to add, on the Airbus the load sheet calculates our MACZFW and MACTOW for take-off. This is then entered into the FMS (MACZFW) on the INIT page and the MACTOW is then dialled onto the pitch trim wheel. Once done it is left well alone in flight)