Here we investigated variation in DNA methylation associated with a germline heterozygous DNMT3A missense pathogenic variant c.2312G > A; p.(Arg771Gln), affecting the catalytic MTase domain, in a large Amish family comprising four children with TBRS, unaffected siblings, and their mosaic father who displayed an intermediate clinical phenotype (Xin et al. 2017). This evidence concerns the gene DNMT3A and Tatton-Brown-Rahman overgrowth syndrome.