Five patients with DCM from three unrelated families in Spain, the USA, and China have been found to carry the same variant, c.80G > A (p.Gly27Asp), in RPL3L, demonstrating a mutational hotspot of RPL3L. According to the ACMG/AMP standards and guidelines [8], the novel c.1074dupA (p.Ala359fs*6) variant is pathogenic based on the PVS1, PM2_supporting, and PM3 criteria, while the c.80G > A (p.Gly27Asp) variant is pathogenic according to the PS2, PM1, PM2_supporting, PM3_Strong, and PP3 criteria. Here, RPL3L is linked to familial dilated cardiomyopathy.