The subsequent development and optimization of next-generation sequencing (NGS) technologies and computational tools was a contributing factor to advances in genome-wide analyses, such as whole-exome sequencing (WES). WES represents an efficient and cost-effective strategy for dismembering the genetic basis and traits of diseases. This approach has proven effective, as it has achieved results that were unattainable through traditional gene discovery strategies. The purpose of this study was to identify pathogenic genetic variants in triple-negative breast cancer TNBC patients via WES. We performed bioinformatics analysis to detect single nucleotide polymorphisms (SNPs) and indels in WES DNA sequences from 4 TNBC samples that are publicly available. The raw reads were aligned to the GRCh38 human reference genome via the Burrows–Wheeler Aligner. BAM files were sorted, and duplicates were marked via SAM tools and Sambamba. Variants were called with Strelka and annotated via the Variant Effect Predictor (VEP). Population frequencies were added from the gnomAD exome and genome databases. ClinVar, SIFT, and PolyPhen were used to assess clinical significance and impact. A total of 21,053 variants were identified: 82.7% SNVs, 6.8% deletions, 4.9% insertions, and 5.6% sequence alterations. Most of the variants had a low impact (58.1%), whereas the other variants had moderate and high impacts (41.9%). Significant deleterious variants were found in the TP53, NF1, and BRCA1/BRCA2 genes. These findings enhance the molecular understanding of TNBC and highlight candidate genes for further investigation. Functional validation is still needed to elucidate their roles in tumor development and therapeutic potential.