diff --git a/src/compiler/checker.ts b/src/compiler/checker.ts
index 0991030bff6cc..8e95c8b3bfc3e 100644
--- a/src/compiler/checker.ts
+++ b/src/compiler/checker.ts
@@ -22914,7 +22914,7 @@ export function createTypeChecker(host: TypeCheckerHost): TypeChecker {
                 // of the much more expensive N * M comparison matrix we explore below. We erase type parameters
                 // as they are known to always be the same.
                 for (let i = 0; i < targetSignatures.length; i++) {
-                    const related = signatureRelatedTo(sourceSignatures[i], targetSignatures[i], /*erase*/ true, reportErrors, intersectionState, incompatibleReporter(sourceSignatures[i], targetSignatures[i]));
+                    const related = signatureRelatedTo(sourceSignatures[i], targetSignatures[i], /*erase*/ !inVarianceComputation, reportErrors, intersectionState, incompatibleReporter(sourceSignatures[i], targetSignatures[i]));
                     if (!related) {
                         return Ternary.False;
                     }
diff --git a/src/compiler/corePublic.ts b/src/compiler/corePublic.ts
index c026d2c741f79..9020af6f7b300 100644
--- a/src/compiler/corePublic.ts
+++ b/src/compiler/corePublic.ts
@@ -15,11 +15,11 @@ export interface MapLike<T> {
     [index: string]: T;
 }
 
-export interface SortedReadonlyArray<T> extends ReadonlyArray<T> {
+export interface SortedReadonlyArray<out T> extends ReadonlyArray<T> {
     " __sortedArrayBrand": any;
 }
 
-export interface SortedArray<T> extends Array<T> {
+export interface SortedArray<out T> extends Array<T> {
     " __sortedArrayBrand": any;
 }
 
diff --git a/src/compiler/types.ts b/src/compiler/types.ts
index 1f796f8b2a0da..f8b836fff36d5 100644
--- a/src/compiler/types.ts
+++ b/src/compiler/types.ts
@@ -1535,12 +1535,12 @@ export type HasContainerFlags =
     | IsObjectLiteralOrClassExpressionMethodOrAccessor;
 
 /** @internal */
-export interface MutableNodeArray<T extends Node> extends Array<T>, TextRange {
+export interface MutableNodeArray<out T extends Node> extends Array<T>, TextRange {
     hasTrailingComma: boolean;
     /** @internal */ transformFlags: TransformFlags; // Flags for transforms, possibly undefined
 }
 
-export interface NodeArray<T extends Node> extends ReadonlyArray<T>, ReadonlyTextRange {
+export interface NodeArray<out T extends Node> extends ReadonlyArray<T>, ReadonlyTextRange {
     readonly hasTrailingComma: boolean;
     /** @internal */ transformFlags: TransformFlags; // Flags for transforms, possibly undefined
 }
diff --git a/tests/baselines/reference/api/typescript.d.ts b/tests/baselines/reference/api/typescript.d.ts
index 4cd20ac817878..c23ba55b3902c 100644
--- a/tests/baselines/reference/api/typescript.d.ts
+++ b/tests/baselines/reference/api/typescript.d.ts
@@ -4145,10 +4145,10 @@ declare namespace ts {
     interface MapLike<T> {
         [index: string]: T;
     }
-    interface SortedReadonlyArray<T> extends ReadonlyArray<T> {
+    interface SortedReadonlyArray<out T> extends ReadonlyArray<T> {
         " __sortedArrayBrand": any;
     }
-    interface SortedArray<T> extends Array<T> {
+    interface SortedArray<out T> extends Array<T> {
         " __sortedArrayBrand": any;
     }
     type Path = string & {
@@ -4889,7 +4889,7 @@ declare namespace ts {
     type HasExpressionInitializer = VariableDeclaration | ParameterDeclaration | BindingElement | PropertyDeclaration | PropertyAssignment | EnumMember;
     type HasDecorators = ParameterDeclaration | PropertyDeclaration | MethodDeclaration | GetAccessorDeclaration | SetAccessorDeclaration | ClassExpression | ClassDeclaration;
     type HasModifiers = TypeParameterDeclaration | ParameterDeclaration | ConstructorTypeNode | PropertySignature | PropertyDeclaration | MethodSignature | MethodDeclaration | ConstructorDeclaration | GetAccessorDeclaration | SetAccessorDeclaration | IndexSignatureDeclaration | FunctionExpression | ArrowFunction | ClassExpression | VariableStatement | FunctionDeclaration | ClassDeclaration | InterfaceDeclaration | TypeAliasDeclaration | EnumDeclaration | ModuleDeclaration | ImportEqualsDeclaration | ImportDeclaration | ExportAssignment | ExportDeclaration;
-    interface NodeArray<T extends Node> extends ReadonlyArray<T>, ReadonlyTextRange {
+    interface NodeArray<out T extends Node> extends ReadonlyArray<T>, ReadonlyTextRange {
         readonly hasTrailingComma: boolean;
     }
     interface Token<TKind extends SyntaxKind> extends Node {
diff --git a/tests/baselines/reference/complexRecursiveCollections.errors.txt b/tests/baselines/reference/complexRecursiveCollections.errors.txt
index 3f51359243a8f..020147b964bd7 100644
--- a/tests/baselines/reference/complexRecursiveCollections.errors.txt
+++ b/tests/baselines/reference/complexRecursiveCollections.errors.txt
@@ -1,3 +1,11 @@
+immutable.ts(305,22): error TS2430: Interface 'Set<T>' incorrectly extends interface 'Seq<never, T>'.
+  The types of 'map(...).filter(...).concat(...).toMap().toSeq().toOrderedMap().keySeq().toMap().mapKeys(...).toSeq().toOrderedMap().toSet().union' are incompatible between these types.
+    Type '(...collections: (never[] | Collection<any, never>)[]) => Set<never>' is not assignable to type '(...collections: (any[] | Collection<any, any>)[]) => Set<any>'.
+      Types of parameters 'collections' and 'collections' are incompatible.
+        Type 'any[] | Collection<any, any>' is not assignable to type 'never[] | Collection<any, never>'.
+          Type 'any[]' is not assignable to type 'never[] | Collection<any, never>'.
+            Type 'any[]' is not assignable to type 'never[]'.
+              Type 'any' is not assignable to type 'never'.
 immutable.ts(341,22): error TS2430: Interface 'Keyed<K, V>' incorrectly extends interface 'Collection<K, V>'.
   The types returned by 'toSeq()' are incompatible between these types.
     Type 'Keyed<K, V>' is not assignable to type 'this'.
@@ -33,7 +41,7 @@ immutable.ts(391,22): error TS2430: Interface 'Set<T>' incorrectly extends inter
         flatMap<M>(mapper: (value: T, key: void, iter: this) => Ara<M>, context?: any): N2<M>;
         toSeq(): N2<T>;
     }
-==== immutable.ts (3 errors) ====
+==== immutable.ts (4 errors) ====
     // Test that complex recursive collections can pass the `extends` assignability check without
     // running out of memory. This bug was exposed in Typescript 2.4 when more generic signatures
     // started being checked.
@@ -339,6 +347,15 @@ immutable.ts(391,22): error TS2430: Interface 'Set<T>' incorrectly extends inter
         export function Set<T>(): Seq.Set<T>;
         export function Set<T>(collection: Iterable<T>): Seq.Set<T>;
         export interface Set<T> extends Seq<never, T>, Collection.Set<T> {
+                         ~~~
+!!! error TS2430: Interface 'Set<T>' incorrectly extends interface 'Seq<never, T>'.
+!!! error TS2430:   The types of 'map(...).filter(...).concat(...).toMap().toSeq().toOrderedMap().keySeq().toMap().mapKeys(...).toSeq().toOrderedMap().toSet().union' are incompatible between these types.
+!!! error TS2430:     Type '(...collections: (never[] | Collection<any, never>)[]) => Set<never>' is not assignable to type '(...collections: (any[] | Collection<any, any>)[]) => Set<any>'.
+!!! error TS2430:       Types of parameters 'collections' and 'collections' are incompatible.
+!!! error TS2430:         Type 'any[] | Collection<any, any>' is not assignable to type 'never[] | Collection<any, never>'.
+!!! error TS2430:           Type 'any[]' is not assignable to type 'never[] | Collection<any, never>'.
+!!! error TS2430:             Type 'any[]' is not assignable to type 'never[]'.
+!!! error TS2430:               Type 'any' is not assignable to type 'never'.
           toJS(): Array<any>;
           toJSON(): Array<T>;
           toSeq(): this;
diff --git a/tests/baselines/reference/complexRecursiveCollections.types b/tests/baselines/reference/complexRecursiveCollections.types
index 0aa394d46b370..2a6a5c12d81a7 100644
--- a/tests/baselines/reference/complexRecursiveCollections.types
+++ b/tests/baselines/reference/complexRecursiveCollections.types
@@ -1139,7 +1139,7 @@ declare module Immutable {
 >Seq : typeof Seq
 
     function isSeq(maybeSeq: any): maybeSeq is Seq.Indexed<any> | Seq.Keyed<any, any>;
->isSeq : (maybeSeq: any) => maybeSeq is Indexed<any> | Keyed<any, any>
+>isSeq : (maybeSeq: any) => maybeSeq is Keyed<any, any> | Indexed<any>
 >maybeSeq : any
 >Seq : any
 >Seq : any
diff --git a/tests/baselines/reference/conditionalTypes2.errors.txt b/tests/baselines/reference/conditionalTypes2.errors.txt
index ef0eab5c43e39..b6923c597cf65 100644
--- a/tests/baselines/reference/conditionalTypes2.errors.txt
+++ b/tests/baselines/reference/conditionalTypes2.errors.txt
@@ -33,9 +33,16 @@ conditionalTypes2.ts(74,12): error TS2345: Argument of type 'Extract<T, Foo & Ba
 conditionalTypes2.ts(75,12): error TS2345: Argument of type 'Extract2<T, Foo, Bar>' is not assignable to parameter of type '{ foo: string; bat: string; }'.
   Type 'T extends Bar ? T : never' is not assignable to type '{ foo: string; bat: string; }'.
     Property 'bat' is missing in type 'Bar & Foo' but required in type '{ foo: string; bat: string; }'.
+conditionalTypes2.ts(91,5): error TS2416: Property 'tail' in type 'Vector<T>' is not assignable to the same property in base type 'Seq<T>'.
+  Type '() => Opt<Vector<T>>' is not assignable to type '() => Opt<Seq<T>>'.
+    Call signature return types 'Opt<Vector<T>>' and 'Opt<Seq<T>>' are incompatible.
+      The types returned by 'toVector().tail().toVector()' are incompatible between these types.
+        Type 'Vector<Vector<Vector<T>>>' is not assignable to type 'Vector<Vector<Seq<T>>>'.
+          Type 'Vector<Seq<T>>' is not assignable to type 'Vector<Vector<T>>'.
+conditionalTypes2.ts(94,5): error TS2394: This overload signature is not compatible with its implementation signature.
 
 
-==== conditionalTypes2.ts (7 errors) ====
+==== conditionalTypes2.ts (9 errors) ====
     interface Covariant<T> {
         foo: T extends string ? T : number;
     }
@@ -177,9 +184,19 @@ conditionalTypes2.ts(75,12): error TS2345: Argument of type 'Extract2<T, Foo, Ba
     
     class Vector<T> implements Seq<T> {
         tail(): Opt<Vector<T>> {
+        ~~~~
+!!! error TS2416: Property 'tail' in type 'Vector<T>' is not assignable to the same property in base type 'Seq<T>'.
+!!! error TS2416:   Type '() => Opt<Vector<T>>' is not assignable to type '() => Opt<Seq<T>>'.
+!!! error TS2416:     Call signature return types 'Opt<Vector<T>>' and 'Opt<Seq<T>>' are incompatible.
+!!! error TS2416:       The types returned by 'toVector().tail().toVector()' are incompatible between these types.
+!!! error TS2416:         Type 'Vector<Vector<Vector<T>>>' is not assignable to type 'Vector<Vector<Seq<T>>>'.
+!!! error TS2416:           Type 'Vector<Seq<T>>' is not assignable to type 'Vector<Vector<T>>'.
             return <any>undefined;
         }
         partition2<U extends T>(predicate:(v:T)=>v is U): [Vector<U>,Vector<Exclude<T, U>>];
+        ~~~~~~~~~~
+!!! error TS2394: This overload signature is not compatible with its implementation signature.
+!!! related TS2750 conditionalTypes2.ts:96:5: The implementation signature is declared here.
         partition2(predicate:(x:T)=>boolean): [Vector<T>,Vector<T>];
         partition2<U extends T>(predicate:(v:T)=>boolean): [Vector<U>,Vector<any>] {
             return <any>undefined;
diff --git a/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.errors.txt b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.errors.txt
new file mode 100644
index 0000000000000..625a942321cb1
--- /dev/null
+++ b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.errors.txt
@@ -0,0 +1,74 @@
+genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts(9,5): error TS2322: Type 'Fn<T2>' is not assignable to type 'Fn<T1>'.
+  Type 'T1' is not assignable to type 'T2'.
+    'T2' could be instantiated with an arbitrary type which could be unrelated to 'T1'.
+genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts(10,5): error TS2322: Type 'Fn<T1>' is not assignable to type 'Fn<T2>'.
+  Type 'T2' is not assignable to type 'T1'.
+    'T1' could be instantiated with an arbitrary type which could be unrelated to 'T2'.
+genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts(12,5): error TS2322: Type 'Concrete2' is not assignable to type 'Concrete1'.
+  Types of parameters 'x' and 'x' are incompatible.
+    Type 'U' is not assignable to type 'string'.
+      Type 'number' is not assignable to type 'string'.
+genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts(13,5): error TS2322: Type 'Concrete1' is not assignable to type 'Concrete2'.
+  Types of parameters 'x' and 'x' are incompatible.
+    Type 'U' is not assignable to type 'number'.
+      Type 'string' is not assignable to type 'number'.
+genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts(15,5): error TS2322: Type 'Concrete1' is not assignable to type 'Fn<T1>'.
+  Types of parameters 'x' and 'x' are incompatible.
+    Type 'U' is not assignable to type 'number'.
+      Type 'T1' is not assignable to type 'number'.
+genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts(16,5): error TS2322: Type 'Fn<T1>' is not assignable to type 'Concrete1'.
+  Types of parameters 'x' and 'x' are incompatible.
+    Type 'U' is not assignable to type 'T1'.
+      'T1' could be instantiated with an arbitrary type which could be unrelated to 'U'.
+
+
+==== genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts (6 errors) ====
+    type Fn<T> = <U extends T>(x: U) => U;
+    
+    type Concrete1 = <U extends number>(x: U) => U;
+    type Concrete2 = <U extends string>(x: U) => U;
+    
+    function f<T1, T2>(t1: Fn<T1>, t2: Fn<T2>, c1: Concrete1, c2: Concrete2) {
+        // every single one of these assignments should error
+    
+        t1 = t2;
+        ~~
+!!! error TS2322: Type 'Fn<T2>' is not assignable to type 'Fn<T1>'.
+!!! error TS2322:   Type 'T1' is not assignable to type 'T2'.
+!!! error TS2322:     'T2' could be instantiated with an arbitrary type which could be unrelated to 'T1'.
+!!! related TS2208 genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts:6:12: This type parameter might need an `extends T2` constraint.
+        t2 = t1;
+        ~~
+!!! error TS2322: Type 'Fn<T1>' is not assignable to type 'Fn<T2>'.
+!!! error TS2322:   Type 'T2' is not assignable to type 'T1'.
+!!! error TS2322:     'T1' could be instantiated with an arbitrary type which could be unrelated to 'T2'.
+!!! related TS2208 genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts:6:16: This type parameter might need an `extends T1` constraint.
+    
+        c1 = c2;
+        ~~
+!!! error TS2322: Type 'Concrete2' is not assignable to type 'Concrete1'.
+!!! error TS2322:   Types of parameters 'x' and 'x' are incompatible.
+!!! error TS2322:     Type 'U' is not assignable to type 'string'.
+!!! error TS2322:       Type 'number' is not assignable to type 'string'.
+        c2 = c1;
+        ~~
+!!! error TS2322: Type 'Concrete1' is not assignable to type 'Concrete2'.
+!!! error TS2322:   Types of parameters 'x' and 'x' are incompatible.
+!!! error TS2322:     Type 'U' is not assignable to type 'number'.
+!!! error TS2322:       Type 'string' is not assignable to type 'number'.
+    
+        t1 = c1;
+        ~~
+!!! error TS2322: Type 'Concrete1' is not assignable to type 'Fn<T1>'.
+!!! error TS2322:   Types of parameters 'x' and 'x' are incompatible.
+!!! error TS2322:     Type 'U' is not assignable to type 'number'.
+!!! error TS2322:       Type 'T1' is not assignable to type 'number'.
+!!! related TS2208 genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts:6:12: This type parameter might need an `extends number` constraint.
+        c1 = t1;
+        ~~
+!!! error TS2322: Type 'Fn<T1>' is not assignable to type 'Concrete1'.
+!!! error TS2322:   Types of parameters 'x' and 'x' are incompatible.
+!!! error TS2322:     Type 'U' is not assignable to type 'T1'.
+!!! error TS2322:       'T1' could be instantiated with an arbitrary type which could be unrelated to 'U'.
+    }
+    
\ No newline at end of file
diff --git a/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.js b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.js
new file mode 100644
index 0000000000000..4b5a028f79506
--- /dev/null
+++ b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.js
@@ -0,0 +1,33 @@
+//// [tests/cases/compiler/genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts] ////
+
+//// [genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts]
+type Fn<T> = <U extends T>(x: U) => U;
+
+type Concrete1 = <U extends number>(x: U) => U;
+type Concrete2 = <U extends string>(x: U) => U;
+
+function f<T1, T2>(t1: Fn<T1>, t2: Fn<T2>, c1: Concrete1, c2: Concrete2) {
+    // every single one of these assignments should error
+
+    t1 = t2;
+    t2 = t1;
+
+    c1 = c2;
+    c2 = c1;
+
+    t1 = c1;
+    c1 = t1;
+}
+
+
+//// [genericSignaturesConstrainedToDifferingGenericsNotCompatible.js]
+"use strict";
+function f(t1, t2, c1, c2) {
+    // every single one of these assignments should error
+    t1 = t2;
+    t2 = t1;
+    c1 = c2;
+    c2 = c1;
+    t1 = c1;
+    c1 = t1;
+}
diff --git a/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.symbols b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.symbols
new file mode 100644
index 0000000000000..f7b53cd99f5ff
--- /dev/null
+++ b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.symbols
@@ -0,0 +1,68 @@
+//// [tests/cases/compiler/genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts] ////
+
+=== genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts ===
+type Fn<T> = <U extends T>(x: U) => U;
+>Fn : Symbol(Fn, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 0))
+>T : Symbol(T, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 8))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 14))
+>T : Symbol(T, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 8))
+>x : Symbol(x, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 27))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 14))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 14))
+
+type Concrete1 = <U extends number>(x: U) => U;
+>Concrete1 : Symbol(Concrete1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 38))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 2, 18))
+>x : Symbol(x, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 2, 36))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 2, 18))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 2, 18))
+
+type Concrete2 = <U extends string>(x: U) => U;
+>Concrete2 : Symbol(Concrete2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 2, 47))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 3, 18))
+>x : Symbol(x, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 3, 36))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 3, 18))
+>U : Symbol(U, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 3, 18))
+
+function f<T1, T2>(t1: Fn<T1>, t2: Fn<T2>, c1: Concrete1, c2: Concrete2) {
+>f : Symbol(f, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 3, 47))
+>T1 : Symbol(T1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 11))
+>T2 : Symbol(T2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 14))
+>t1 : Symbol(t1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 19))
+>Fn : Symbol(Fn, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 0))
+>T1 : Symbol(T1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 11))
+>t2 : Symbol(t2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 30))
+>Fn : Symbol(Fn, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 0))
+>T2 : Symbol(T2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 14))
+>c1 : Symbol(c1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 42))
+>Concrete1 : Symbol(Concrete1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 0, 38))
+>c2 : Symbol(c2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 57))
+>Concrete2 : Symbol(Concrete2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 2, 47))
+
+    // every single one of these assignments should error
+
+    t1 = t2;
+>t1 : Symbol(t1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 19))
+>t2 : Symbol(t2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 30))
+
+    t2 = t1;
+>t2 : Symbol(t2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 30))
+>t1 : Symbol(t1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 19))
+
+    c1 = c2;
+>c1 : Symbol(c1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 42))
+>c2 : Symbol(c2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 57))
+
+    c2 = c1;
+>c2 : Symbol(c2, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 57))
+>c1 : Symbol(c1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 42))
+
+    t1 = c1;
+>t1 : Symbol(t1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 19))
+>c1 : Symbol(c1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 42))
+
+    c1 = t1;
+>c1 : Symbol(c1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 42))
+>t1 : Symbol(t1, Decl(genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts, 5, 19))
+}
+
diff --git a/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.types b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.types
new file mode 100644
index 0000000000000..ff1623d9bd842
--- /dev/null
+++ b/tests/baselines/reference/genericSignaturesConstrainedToDifferingGenericsNotCompatible.types
@@ -0,0 +1,55 @@
+//// [tests/cases/compiler/genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts] ////
+
+=== genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts ===
+type Fn<T> = <U extends T>(x: U) => U;
+>Fn : Fn<T>
+>x : U
+
+type Concrete1 = <U extends number>(x: U) => U;
+>Concrete1 : <U extends number>(x: U) => U
+>x : U
+
+type Concrete2 = <U extends string>(x: U) => U;
+>Concrete2 : <U extends string>(x: U) => U
+>x : U
+
+function f<T1, T2>(t1: Fn<T1>, t2: Fn<T2>, c1: Concrete1, c2: Concrete2) {
+>f : <T1, T2>(t1: Fn<T1>, t2: Fn<T2>, c1: Concrete1, c2: Concrete2) => void
+>t1 : Fn<T1>
+>t2 : Fn<T2>
+>c1 : Concrete1
+>c2 : Concrete2
+
+    // every single one of these assignments should error
+
+    t1 = t2;
+>t1 = t2 : Fn<T2>
+>t1 : Fn<T1>
+>t2 : Fn<T2>
+
+    t2 = t1;
+>t2 = t1 : Fn<T1>
+>t2 : Fn<T2>
+>t1 : Fn<T1>
+
+    c1 = c2;
+>c1 = c2 : Concrete2
+>c1 : Concrete1
+>c2 : Concrete2
+
+    c2 = c1;
+>c2 = c1 : Concrete1
+>c2 : Concrete2
+>c1 : Concrete1
+
+    t1 = c1;
+>t1 = c1 : Concrete1
+>t1 : Fn<T1>
+>c1 : Concrete1
+
+    c1 = t1;
+>c1 = t1 : Fn<T1>
+>c1 : Concrete1
+>t1 : Fn<T1>
+}
+
diff --git a/tests/baselines/reference/styledComponentsInstantiaionLimitNotReached.errors.txt b/tests/baselines/reference/styledComponentsInstantiaionLimitNotReached.errors.txt
new file mode 100644
index 0000000000000..2d5c3c0d0545b
--- /dev/null
+++ b/tests/baselines/reference/styledComponentsInstantiaionLimitNotReached.errors.txt
@@ -0,0 +1,207 @@
+styledComponentsInstantiaionLimitNotReached.ts(171,8): error TS2615: Type of property 'propTypes' circularly references itself in mapped type 'ForwardRefExoticBase<Omit<Omit<any, any> & Partial<Pick<any, any>>, "theme"> & { theme?: any; } & WithChildrenIfReactComponentClass<StyledComponentInnerComponent<WithC>>>'.
+
+
+==== styledComponentsInstantiaionLimitNotReached.ts (1 errors) ====
+    /// <reference path="/.lib/react16.d.ts" />
+    import * as React from "react";
+    
+    interface REACT_STATICS {
+        childContextTypes: true;
+        contextType: true;
+        contextTypes: true;
+        defaultProps: true;
+        displayName: true;
+        getDefaultProps: true;
+        getDerivedStateFromError: true;
+        getDerivedStateFromProps: true;
+        mixins: true;
+        propTypes: true;
+        type: true;
+    }
+    
+    interface KNOWN_STATICS {
+        name: true;
+        length: true;
+        prototype: true;
+        caller: true;
+        callee: true;
+        arguments: true;
+        arity: true;
+    }
+    
+    interface MEMO_STATICS {
+        '$$typeof': true;
+        compare: true;
+        defaultProps: true;
+        displayName: true;
+        propTypes: true;
+        type: true;
+    }
+    
+    interface FORWARD_REF_STATICS {
+        '$$typeof': true;
+        render: true;
+        defaultProps: true;
+        displayName: true;
+        propTypes: true;
+    }
+    
+    
+    type NonReactStatics<
+        S extends React.ComponentType<any>,
+        C extends {
+            [key: string]: true
+        } = {}
+        > = {
+            [key in Exclude<
+                keyof S,
+                S extends React.MemoExoticComponent<any>
+                ? keyof MEMO_STATICS | keyof C
+                : S extends React.ForwardRefExoticComponent<any>
+                ? keyof FORWARD_REF_STATICS | keyof C
+                : keyof REACT_STATICS | keyof KNOWN_STATICS | keyof C
+            >]: S[key]
+        };
+    
+    export type AnyStyledComponent = StyledComponent<any, any, any, any> | StyledComponent<any, any, any>;
+    export type StyledComponent<
+        C extends keyof JSX.IntrinsicElements | React.ComponentType<any>,
+        T extends object,
+        O extends object = {},
+        A extends keyof any = never
+        > = // the "string" allows this to be used as an object key
+        // I really want to avoid this if possible but it's the only way to use nesting with object styles...
+        string &
+        StyledComponentBase<C, T, O, A> &
+        NonReactStatics<C extends React.ComponentType<any> ? C : never>;
+    
+    export type StyledComponentProps<
+        // The Component from whose props are derived
+        C extends string | React.ComponentType<any>,
+        // The Theme from the current context
+        T extends object,
+        // The other props added by the template
+        O extends object,
+        // The props that are made optional by .attrs
+        A extends keyof any
+        > =
+        // Distribute O if O is a union type
+        O extends object
+        ? WithOptionalTheme<
+            Omit<
+                ReactDefaultizedProps<
+                    C,
+                    React.ComponentPropsWithRef<
+                        C extends IntrinsicElementsKeys | React.ComponentType<any> ? C : never
+                    >
+                > &
+                O,
+                A
+            > &
+            Partial<
+                Pick<
+                    React.ComponentPropsWithRef<
+                        C extends IntrinsicElementsKeys | React.ComponentType<any> ? C : never
+                    > &
+                    O,
+                    A
+                >
+            >,
+            T
+        > &
+        WithChildrenIfReactComponentClass<C>
+        : never;
+    
+    type Defaultize<P, D> = P extends any
+        ? string extends keyof P
+        ? P
+        : Pick<P, Exclude<keyof P, keyof D>> &
+        Partial<Pick<P, Extract<keyof P, keyof D>>> &
+        Partial<Pick<D, Exclude<keyof D, keyof P>>>
+        : never;
+    
+    type ReactDefaultizedProps<C, P> = C extends { defaultProps: infer D } ? Defaultize<P, D> : P;
+    
+    type WithChildrenIfReactComponentClass<C extends string | React.ComponentType<any>> = C extends React.ComponentClass<
+        any
+    >
+        ? { children?: React.ReactNode }
+        : {};
+    export type IntrinsicElementsKeys = keyof JSX.IntrinsicElements;
+    type WithOptionalTheme<P extends { theme?: T }, T> = Omit<P, 'theme'> & {
+        theme?: T;
+    };
+    
+    type ForwardRefExoticBase<P> = Pick<React.ForwardRefExoticComponent<P>, keyof React.ForwardRefExoticComponent<any>>;
+    
+    type StyledComponentPropsWithAs<
+        C extends string | React.ComponentType<any>,
+        T extends object,
+        O extends object,
+        A extends keyof any,
+        F extends string | React.ComponentType<any> = C
+        > = StyledComponentProps<C, T, O, A> & { as?: C; forwardedAs?: F };
+    
+    export type StyledComponentInnerOtherProps<C extends AnyStyledComponent> = C extends StyledComponent<
+        any,
+        any,
+        infer O,
+        any
+    >
+        ? O
+        : C extends StyledComponent<any, any, infer O>
+        ? O
+        : never;
+    export type StyledComponentInnerAttrs<C extends AnyStyledComponent> = C extends StyledComponent<any, any, any, infer A>
+        ? A
+        : never;
+    
+    export interface StyledComponentBase<
+        C extends string | React.ComponentType<any>,
+        T extends object,
+        O extends object = {},
+        A extends keyof any = never
+        > extends ForwardRefExoticBase<StyledComponentProps<C, T, O, A>> {
+        // add our own fake call signature to implement the polymorphic 'as' prop
+        (props: StyledComponentProps<C, T, O, A> & { as?: never; forwardedAs?: never }): React.ReactElement<
+            StyledComponentProps<C, T, O, A>
+        >;
+        <AsC extends string | React.ComponentType<any> = C, FAsC extends string | React.ComponentType<any> = AsC>(
+            props: StyledComponentPropsWithAs<AsC, T, O, A, FAsC>,
+        ): React.ReactElement<StyledComponentPropsWithAs<AsC, T, O, A, FAsC>>;
+    
+        withComponent<WithC extends AnyStyledComponent>(
+            component: WithC,
+        ): StyledComponent<
+           ~~~~~~~~~~~~~~~~
+            StyledComponentInnerComponent<WithC>,
+    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+            T,
+    ~~~~~~~~~~
+            O & StyledComponentInnerOtherProps<WithC>,
+    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+            A | StyledComponentInnerAttrs<WithC>
+    ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+        >;
+    ~~~~~
+!!! error TS2615: Type of property 'propTypes' circularly references itself in mapped type 'ForwardRefExoticBase<Omit<Omit<any, any> & Partial<Pick<any, any>>, "theme"> & { theme?: any; } & WithChildrenIfReactComponentClass<StyledComponentInnerComponent<WithC>>>'.
+        withComponent<WithC extends keyof JSX.IntrinsicElements | React.ComponentType<any>>(
+            component: WithC,
+        ): StyledComponent<WithC, T, O, A>;
+    }
+    
+    export type StyledComponentInnerComponent<C extends React.ComponentType<any>> = C extends StyledComponent<
+        infer I,
+        any,
+        any,
+        any
+    >
+        ? I
+        : C extends StyledComponent<infer I, any, any>
+        ? I
+        : C;
+    export type StyledComponentPropsWithRef<
+        C extends keyof JSX.IntrinsicElements | React.ComponentType<any>
+        > = C extends AnyStyledComponent
+        ? React.ComponentPropsWithRef<StyledComponentInnerComponent<C>> // shouldn't have an instantiation limit error
+        : React.ComponentPropsWithRef<C>;
\ No newline at end of file
diff --git a/tests/cases/compiler/genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts b/tests/cases/compiler/genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts
new file mode 100644
index 0000000000000..3889f646205cb
--- /dev/null
+++ b/tests/cases/compiler/genericSignaturesConstrainedToDifferingGenericsNotCompatible.ts
@@ -0,0 +1,18 @@
+// @strict: true
+type Fn<T> = <U extends T>(x: U) => U;
+
+type Concrete1 = <U extends number>(x: U) => U;
+type Concrete2 = <U extends string>(x: U) => U;
+
+function f<T1, T2>(t1: Fn<T1>, t2: Fn<T2>, c1: Concrete1, c2: Concrete2) {
+    // every single one of these assignments should error
+
+    t1 = t2;
+    t2 = t1;
+
+    c1 = c2;
+    c2 = c1;
+
+    t1 = c1;
+    c1 = t1;
+}