A method of detecting presence of a nucleotide variant in a target nucleic acid molecule in a sample, comprising: contacting the sample with at least two probes complementary to the same strand of the target nucleic acid molecule, wherein the target nucleic acid molecule comprises a nucleotide variant under conditions sufficient for the first probe and the second probe to hybridize to the target nucleic acid molecule, producing a mixture of hybridized nucleic acid molecules and unhybridized nucleic acid molecules, and wherein each probe comprises a detectable label at the end of the probe or within two bases of the nucleotide variant position, wherein the first probe is complementary to wild type at the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid molecule nucleotide variant position is two to six bases from a 3'-end of the first probe, and wherein the second probe is complementary to a first variant for the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid nucleotide variant position is two to six bases from a 5'-end of the second probe, and wherein the first and the second probe overlap at the 3'-end of the first probe and the 5'-end of the second probe in the region of the variant position; or wherein the first probe is complementary to wild type at the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid molecule nucleotide variant position is two to six bases from a 5'-end of the first probe, wherein the second probe is complementary to a first variant for the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid nucleotide variant position is two to six bases from a 3'-end of the second probe, and wherein the first and the second probe overlap at the 5'-end of the first probe and the 3'-end of the second probe in the region of the variant position; contacting the mixture of hybridized nucleic acid molecules and unhybridized nucleic acid molecules with a nuclease specific for single-stranded nucleic acid molecules under conditions sufficient to digest and remove the unhybridized nucleic acid molecules containing mismatches with the target nucleic acid molecule; and detecting presence of one or more of the probes remaining in the mixture following nuclease treatment, thereby detecting presence of the nucleotide variant in the sample, optionally further comprising lysing the sample. contacting the sample with at least two probes complementary to the same strand of the target nucleic acid molecule, wherein the target nucleic acid molecule comprises a nucleotide variant under conditions sufficient for the first probe and the second probe to hybridize to the target nucleic acid molecule, producing a mixture of hybridized nucleic acid molecules and unhybridized nucleic acid molecules, and wherein each probe comprises a detectable label at the end of the probe or within two bases of the nucleotide variant position, wherein the first probe is complementary to wild type at the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid molecule nucleotide variant position is two to six bases from a 3'-end of the first probe, and wherein the second probe is complementary to a first variant for the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid nucleotide variant position is two to six bases from a 5'-end of the second probe, and wherein the first and the second probe overlap at the 3'-end of the first probe and the 5'-end of the second probe in the region of the variant position; or wherein the first probe is complementary to wild type at the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid molecule nucleotide variant position is two to six bases from a 5'-end of the first probe, wherein the second probe is complementary to a first variant for the target nucleic acid molecule nucleotide variant, wherein the target nucleic acid nucleotide variant position is two to six bases from a 3'-end of the second probe, and wherein the first and the second probe overlap at the 5'-end of the first probe and the 3'-end of the second probe in the region of the variant position; contacting the mixture of hybridized nucleic acid molecules and unhybridized nucleic acid molecules with a nuclease specific for single-stranded nucleic acid molecules under conditions sufficient to digest and remove the unhybridized nucleic acid molecules containing mismatches with the target nucleic acid molecule; and detecting presence of one or more of the probes remaining in the mixture following nuclease treatment, thereby detecting presence of the nucleotide variant in the sample, optionally further comprising lysing the sample.