Proteogenomics is a multi-omics setup combining mass spectrometry and next-generation sequencing (NGS) technologies (using genomics and/or transcriptomics) with main aims of improving genome annotation and facilitating characterization of proteo-isoforms. However, working with proteogenomic approach is a very challenging task as it is generating multi-omics data and integrating these data for interpretation of results for biological or clinical implications. There is an urgent need for the development of protocols for integrated proteogenomics approaches. Genome resequencing yields massive data for missense single-nucleotide polymorphisms (SNP), and SNPs are yet not fully covered for their pathogenic nature using proteogenomic approaches. In this chapter, we present such a protocol for dealing with pathogenic missense SNPs using an integrated proteogenomics pipeline combining several steps: DNA-Seq, RNA-Seq, mass spectroscopy (MS), making customized databases of produced datasets, and screening and filtering for useful MS spectrums. This protocol also provides users with tricks and tips for the modifications, based on the requirements of the projects.