SARS-CoV-2 is a RNA coronavirus of the β-CoVs family responsible for the pandemic of the severe acute respiratory syndrome (COVID-19). It is hypothesized that the viral genome of the contemporary predominant founder clones is likely to be evolving in geographic-dependent manner. Thus, strains of different origin may be characterized by different mutation patterns. The study was aimed to perform the mutational and phylogenetic analysis of the Russian SARS-CoV-2 genomes at different time periods and in various regions, as well as to characterize the mutational profiles of isolates using the bioinformatics approaches. The mutation accumulation was compared in 86 SARS-CoV-2 whole-genome sequences from Russia and 220 from Europe and North America in order to reveal the characteristic gene variations, the possible positive selection patterns. Along with the known mutation variants in the structural proteins genes, typical for isolates of European origin, several additional mutations including the synonymous mutation in gene M (C26750T) characteristic for Russian isolates were revealed. Double mutation R203K and G204R in the nucleocapside gene which previously emerged in Europe began spreading and rapidly (within a month) became the dominant form in Russia. The results obtained indicate that the viral genome of most Russian isolates evolves with accumulation of new mutations associated with increased viral transmission. Data on the SARS-CoV-2 genome specific mutation patterns might be used for the detection of the virus, as well as for tracking and controlling of its spread. © 2020 Pirogov Russian National Research Medical University. All rights reserved.