  We apply the methods recently developed for computation of type IIA disk
instantons using mirror symmetry to a large class of D-branes wrapped over
Lagrangian cycles of non-compact Calabi-Yau 3-folds. Along the way we clarify
the notion of ``flat coordinates'' for the boundary theory. We also discover an
integer IR ambiguity needed to define the quantum theory of D-branes wrapped
over non-compact Lagrangian submanifolds. In the large $N$ dual Chern-Simons
theory, this ambiguity is mapped to the UV choice of the framing of the knot.
In a type IIB dual description involving $(p,q)$ 5-branes, disk instantons of
type IIA get mapped to $(p,q)$ string instantons. The M-theory lift of these
results lead to computation of superpotential terms generated by M2 brane
instantons wrapped over 3-cycles of certain manifolds of $G_2$ holonomy.
