@@ -2225,7 +2225,8 @@ def narrow_type_from_binder(self, expr: Expression, known_type: Type) -> Type:
         if expr.literal >= LITERAL_TYPE:
             restriction = self.chk.binder.get(expr)
             if restriction:
-                return narrow_declared_type(known_type, restriction)
+                ans = narrow_declared_type(known_type, restriction)
+                return ans
         return known_type
 
 
 
@@ -10,7 +10,7 @@
     UninhabitedType, TypeType, true_or_false
 )
 from mypy.maptype import map_instance_to_supertype
-from mypy.subtypes import is_subtype, is_equivalent, is_subtype_ignoring_tvars
+from mypy.subtypes import is_subtype, is_equivalent, is_subtype_ignoring_tvars, is_proper_subtype
 
 from mypy import experiments
 
@@ -29,10 +29,10 @@ def join_simple(declaration: Type, s: Type, t: Type) -> Type:
     if isinstance(s, ErasedType):
         return t
 
-    if is_subtype(s, t):
+    if is_proper_subtype(s, t):
         return t
 
-    if is_subtype(t, s):
+    if is_proper_subtype(t, s):
         return s
 
     if isinstance(declaration, UnionType):
 
@@ -7,6 +7,7 @@
 )
 import mypy.applytype
 import mypy.constraints
+from mypy.erasetype import erase_type
 # Circular import; done in the function instead.
 # import mypy.solve
 from mypy import messages, sametypes
@@ -512,13 +513,22 @@ def unify_generic_callable(type: CallableType, target: CallableType,
 
 
 def restrict_subtype_away(t: Type, s: Type) -> Type:
-    """Return a supertype of (t intersect not s)
+    """Return t minus s.
 
-    Currently just remove elements of a union type.
+    If we can't determine a precise result, return a supertype of the
+    ideal result (just t is a valid result).
+
+    This is used for type inference of runtime type checks such as
+    isinstance.
+
+    Currently this just removes elements of a union type.
     """
     if isinstance(t, UnionType):
-        new_items = [item for item in t.items if (not is_subtype(item, s)
-                                                  or isinstance(item, AnyType))]
+        # Since runtime type checks will ignore type arguments, erase the types.
+        erased_s = erase_type(s)
+        new_items = [item for item in t.items
+                     if (not is_proper_subtype(erase_type(item), erased_s)
+                         or isinstance(item, AnyType))]
         return UnionType.make_union(new_items)
     else:
         return t
@@ -640,6 +650,9 @@ def visit_tuple_type(self, left: TupleType) -> bool:
                 if not right.args:
                     return False
                 iter_type = right.args[0]
+                if is_named_instance(right, 'builtins.tuple') and isinstance(iter_type, AnyType):
+                    # Special case plain 'tuple' which is needed for isinstance(x, tuple).
+                    return True
                 return all(is_proper_subtype(li, iter_type) for li in left.items)
             return is_proper_subtype(left.fallback, right)
         elif isinstance(right, TupleType):
 
@@ -575,3 +575,17 @@ reveal_type(u(a, None))  # E: Revealed type is 'Union[builtins.None, Any]'
 reveal_type(u(None, a))  # E: Revealed type is 'Union[Any, builtins.None]'
 reveal_type(u(1, None))  # E: Revealed type is 'Union[builtins.None, builtins.int*]'
 reveal_type(u(None, 1))  # E: Revealed type is 'Union[builtins.int*, builtins.None]'
+
+[case testIsinstanceAndOptionalAndAnyBase]
+from typing import Any, Optional
+
+class A(Any): pass
+
+def f(a: Optional[A]):
+    reveal_type(a) # E: Revealed type is 'Union[__main__.A, builtins.None]'
+    if a is not None:
+        reveal_type(a) # E: Revealed type is '__main__.A'
+    else:
+        reveal_type(a) # E: Revealed type is 'builtins.None'
+    reveal_type(a) # E: Revealed type is 'Union[__main__.A, builtins.None]'
+[builtins fixtures/isinstance.pyi]