Work flow diagram for the identification of P/LP germ line variants. DNA was extracted from thawed peripheral blood from 404 patients with MDS and was sequenced using an augmented whole-exome sequencing platform. SNVs and CNVs were called in 233 genes, using custom bioinformatic pipelines. A total of 21,661 SNVs and 334 CNVs were manually curated according to the ACMG/AMP and ClinGen SVI-WG guidelines. P/LP germ line variants were validated by Sanger sequencing, subcloning, and/or RT-qPCR. ACMG, American College of Medical Genetics; AMP, Association for Molecular Pathology; ClinGen SVI-WG, Clinical Genome Sequence Variant Interpretation Working Group; CNV, copy number variant; LP, likely pathogenic; MDS, myelodysplastic syndrome; P, pathogenic; RT-qPCR, quantitative real-time PCR; SNV, single-nucleotide variant; WES, whole-exome sequencing.