Herein we report the mutational spectrum of three breast cancer candidate genes (TP53, PIK3CA and PTEN) using WES for identifying potential biomarkers. The WES data was thoroughly analyzed using SAMtools for variant calling and identification of the mutations. Various bioinformatic tools (SIFT, PolyPhen-2, Mutation Taster, ISPRED-SEQ, SAAFEQ-SEQ, ConSurf, PROCHECK etc.) were used to were to determine the pathogenicity and nature of the SNVs. Selected interaction site (IS) mutations were visualized in PyMOL after building 3D structures in Swiss-Model. Ramachandran plots generated by using PROCHECK server. The selected IS mutations were subjected to the molecular dynamic simulation (MDS) studies using Gromacs 4.5. STRING and GeneMANIA were used for the prediction of gene-gene interaction and pathways. Our results revealed that the luminal A molecular subtype of the breast cancer was most common, whereas, a high percentage of was Her2 negatives. Moreover, the somatic mutations were more common as compared to the germline mutations in TP53, PIK3CA and PTEN. 20% of the identified mutations are reported for the 1st time from Khyber Pakhtunkhwa. In the enrolled cohort, 23 mutations were nonsynonymous SNVs. The frequency of mutations was highest in PIK3CA, followed by TP53 and PTEN. A total of 13 mutations were found to be highly pathogenic. Four novel mutations were identified on PIK3CA and one each on PTEN and TP53. SAAFEQ-SEQ predicted destabilizing effect for all mutations. ISPRED-SEQ predicted 9 IS mutations (6 on TP53 & 3 on PIK3CA), whereas no IS mutation was predicted on PTEN. The TP53 IS mutations were TP53R43H, TP53Y73X, TP53K93Q , TP53K93R, TP53D149E, TP53Q199X whereas for PIK3CA, the IS mutations were PIK3CAL156V, PIK3CA M610K and  PIK3CAH1047R. Analysis from the ConSurf webserver revealed five SNVs with highly conserved status (conservation score 9) across TP53 and PTEN. TP53P33R was found predominant in the grade 3 tumors, whereas, PTEN p.C65S was distributed on ER+, ER-, PR+, PR-, Her2+ and Her2- patients. TP53p.P33R mutation was found to be recurring in the 14/19 (73.6%) patients and therefore can be considered as potential biomarker. Finally, these mutations were studied in the context of their potential association with different hormonal and social factors.