[kilink]

...Or can you?

  import ctypes

  def tuple_setitem(t, index, item):
      obj = ctypes.py_object(t)
      item = ctypes.py_object(item)
      ref_count = ctypes.c_long.from_address(id(t))
      original_count = ref_count.value
      if original_count != 1:
          ref_count.value = 1
      ctypes.pythonapi.Py_IncRef(item)
      ctypes.pythonapi.PyTuple_SetItem(obj, ctypes.c_ssize_t(index), item)
      ref_count.value = original_count

  >>> x = (1, 2, 3,)
  >>> tuple_setitem(x, 1, "foo")
  >>> x
  (1, "foo", 3)

Disclaimer: for entertainment purposes only, do not try this at home!