Using two tetraphenylbenzene isomers differing only by the anchoring points to the gold electrodes, we investigate the influence of quantum interference on the single molecule charge transport. The distinct anchor points are realized by selective halogen-mediated binding to the electrodes by formation of surface-stabilized isomers after zzg iodine cleavage. Both isomers are essentially chemically identical and only weakly perturbed by the electrodes avoiding largely parasitic effects, which allows us to focus solely on the relation between quantum interference and the intrinsic molecular properties. The conductance of the two isomers differs by over 1 order of magnitude and is attributed to constructive and destructive interference. Our ab initio based transport calculations compare very well with the accompanying scanning tunneling microscope break junction measurements of the conductance. The findings are rationalized using a two level model, which shows that the interorbital coupling plays decisive role for the interference effects.