A method of detecting mutations in a target sequence of a double stranded DNA molecule (dsDNA), the method comprising: contacting a sample comprising dsDNA with: a forward gene-specific primer comprising a first hemi-functional NGS adapter sequence, and a clamping oligonucleotide that optionally comprises one or more locked nucleotides, wherein the forward primer and clamping oligonucleotide are in cis, and wherein the clamping oligo hybridizes to a wild type sequence of the target gene in a region suspected of comprising one or more mutations; performing a first round of single strand primer extension PCR, to produce a first population of amplicons; purifying the first population of amplicons; contacting the purified amplicons with: a first universal primer complementary to a portion of the first hemi-functional NGS adapter sequence on the purified amplicons, wherein amplification with the primer creates a first fully functional NGS adapter sequence, a reverse gene specific primer comprising a second hemi-functional NGS adapter sequence on the purified amplicons, wherein the reverse primer is in trans with the primer complementary to a portion of the first NGS adapter sequence, and; a second universal primer identical to the second hemi-functional NGS adapter sequence on the reverse primer, wherein amplification with the second universal primer creates a second fully functional NGS adapter sequence; performing a second round of PCR ("PCR2") to complete amplification of a second population of amplicons comprising both first and second fully functional NGS adapter sequences; sequencing the second population of amplicons; and comparing the sequences of the second population of amplicons to a reference wild type target sequence; to thereby detect mutations in the target sequence. contacting a sample comprising dsDNA with: a forward gene-specific primer comprising a first hemi-functional NGS adapter sequence, and a clamping oligonucleotide that optionally comprises one or more locked nucleotides, wherein the forward primer and clamping oligonucleotide are in cis, and wherein the clamping oligo hybridizes to a wild type sequence of the target gene in a region suspected of comprising one or more mutations; a forward gene-specific primer comprising a first hemi-functional NGS adapter sequence, and a clamping oligonucleotide that optionally comprises one or more locked nucleotides, wherein the forward primer and clamping oligonucleotide are in cis, and wherein the clamping oligo hybridizes to a wild type sequence of the target gene in a region suspected of comprising one or more mutations; performing a first round of single strand primer extension PCR, to produce a first population of amplicons; purifying the first population of amplicons; contacting the purified amplicons with: a first universal primer complementary to a portion of the first hemi-functional NGS adapter sequence on the purified amplicons, wherein amplification with the primer creates a first fully functional NGS adapter sequence, a reverse gene specific primer comprising a second hemi-functional NGS adapter sequence on the purified amplicons, wherein the reverse primer is in trans with the primer complementary to a portion of the first NGS adapter sequence, and; a second universal primer identical to the second hemi-functional NGS adapter sequence on the reverse primer, wherein amplification with the second universal primer creates a second fully functional NGS adapter sequence; a first universal primer complementary to a portion of the first hemi-functional NGS adapter sequence on the purified amplicons, wherein amplification with the primer creates a first fully functional NGS adapter sequence, a reverse gene specific primer comprising a second hemi-functional NGS adapter sequence on the purified amplicons, wherein the reverse primer is in trans with the primer complementary to a portion of the first NGS adapter sequence, and; a second universal primer identical to the second hemi-functional NGS adapter sequence on the reverse primer, wherein amplification with the second universal primer creates a second fully functional NGS adapter sequence; performing a second round of PCR ("PCR2") to complete amplification of a second population of amplicons comprising both first and second fully functional NGS adapter sequences; sequencing the second population of amplicons; and comparing the sequences of the second population of amplicons to a reference wild type target sequence; to thereby detect mutations in the target sequence.