Abstract: Described herein are compositions and methods useful for the detection of nucleic acid variations. Ligation within a probe or between probes is used to distinguish between probes perfectly complementary to a target and those containing a mismatch. Nucleotide fill-in/extension steps are optionally applied according to the type of assay performed. A circularization and relinearization step can be applied to create a template for further amplification and detection. In certain aspects, portions of a target sequence or its complement are not amplified.