Although the results between the W2711X filamin‐C knock‐in and the R349P desmin knock‐in mice are not directly comparable due to methodological differences, our findings on myofibrillar lesion formation suggest that both R349P mutant desmin and W2711X mutant filamin‐C exert deleterious effects on the myofibrillar apparatus as a key pathogenic step in these two forms of myofibrillar myopathies. The gene discussed is DES; the disease is myopathy.