Consistency and reproducibility of large panel next-generation sequencing: Multi-laboratory assessment of somatic mutation detection on reference materials with mismatch repair and proofreading deficiency

•Cell lines with MMR and proofreading deficiency were constructed using the CRISPR technology for reference samples.•Paired tumor–normal reference samples close to clinical specimens were prepared.•A reliable process to determine high-confidence region and positive variants was designed.•A multi-laboratory study was conducted to evaluate reproducibility and accuracy of participating panels.•Potential sources of false-discovery were explored for assay optimization.