In 3 unrelated families with familial hypertrophic cardiomyopathy linked to chromosome 1q, including the family originally reported by Watkins et al. (1993), Thierfelder et al. (1994) identified 3 different heterozygous mutations in the TNNT2 gene (191045.0001-191045.0003, respectively). ... In 3 unrelated families with familial hypertrophic cardiomyopathy linked to chromosome 1q, including the family originally reported by Watkins et al. (1993), Thierfelder et al. (1994) identified 3 different heterozygous mutations in the TNNT2 gene (191045.0001-191045.0003, respectively). Watkins et al. (1995) identified 2 heterozygous mutations in the TNNT2 gene in affected members of 2 families with CMH (191045.0004 and 191045.0005, respectively). In 6 of 46 unrelated Japanese CMH families, Anan et al. (1998) found the same F110I mutation in the TNNT2 gene (191045.0005) that had been identified previously by Watkins et al. (1995). Haplotype analysis supported a founder effect in 2 families, whereas the others had independent mutations; the authors suggested that F110I may represent a mutation hotspot. There was considerable inter- and intrafamilial phenotypic variability, with apical hypertrophy alone in 2 unrelated families. In contrast to other reported TNNT2 mutations, F110I appeared to show a favorable prognosis, In a 3-generation family segregating autosomal dominant cardiomyopathy, in which the proband had a restrictive phenotype (RCM3; 612422) and relatives had clinical features of restrictive, hypertrophic, and/or dilated (CDM1D; 601494) cardiomyopathy, Menon et al. (2008) performed targeted linkage analysis for 9 sarcomeric genes and identified heterozygosity for the I79N mutation in the TNNT2 gene (191045.0001), previously reported by Thierfelder et al. (1994) in a family with hypertrophic cardiomyopathy. The mutation segregated with the disease phenotype and was not found in unaffected individuals. Despite the variable morphology, all affected members of the family exhibited restrictive physiology. There was a high incidence of atrial tachyarrhythmia but no significant ventricular arrhythmia or sudden death in affected members of this family.