Global sharing of SARS-CoV-2 sequences enabled comprehensive analyses of COVID-19 genomic diversity and demographics. Yet, regional genomic surveillance is often neglected, leading to the possible oversight of novel mutations by public health authorities. Our study used the Global Initiative on Sharing Avian Influenza Data (GISAID) database to analyse infection patterns in the state of Negeri Sembilan, and compare infection patterns to the state of Selangor, in Malaysia. We discuss the impact of rapid vaccination on resulting single nucleotide variants (SNVs) and identified novel sporadic mutations may affect viral fitness and pathogenicity. Four hundred and seventeen SARS-CoV-2 sequences extracted from Negeri Sembilan from July 2021 until June 2022. Infection patterns based on pangolin lineages from Negeri Sembilan was compared to infections of the same period from Selangor. SNVs from the spike protein were sorted by frequency, with the lowest frequency variant submitted for functional prediction using PredictSNP. Negeri Sembilan exhibited a comparable infection pattern to Selangor, but with fewer Omicron sequences which was postulated to occur due to the rapid vaccination strategies by Negeri Sembilan. Omicron outbreaks were associated with eased lockdowns and policy changes in December 2021. From our extracted data, seventy novel SNVs in the spike protein of SARS-CoV-2 were extracted from this study. In silico predictions indicated five of the SNVs (S221L, L226S, V826L, C1240F and C1243F) to may cause functional defects to the spike protein. Rapid sequencing and analysis will aid policymaking for public health controls by detecting potential outbreaks within transient variants.