With the emergence of different strains of SARS-CoV-2, it is important to develop a fast and simple method of screening for the key mutations. Banada et al. developed a melting temperature assay to identify the SARS-CoV-2 N501Y mutation found specifically in the new variants of the virus (United Kingdom (B.1.1.7), South Africa (B1.351) and Brazil (P.1)). RT-PCR was used to amplify the sequence of the SARS-CoV-2 N501Y mutation. Two sloppy molecular beacon probes (SMB), with unique fluorophores and melting temperatures, were utilized within the PCR assay that distinctly targeted either the wild type (WT) or mutant (MT) sequences. A shift in melting temperatures was used to differentiate between a WT or MT SARS-CoV-2 infection. The assays were validated in 50 patient samples (20 infected, 30 negative controls) and the detection of MT infections was 100% correlated with sanger sequencing. This study represents one of the first uses of a PCR-based “Tm signature” to detect and differentiate the types of SARS-CoV-2 infections. *This article is a preprint in medRxiv and has not yet been peer-reviewed.