ClinVar

Description

p.Thr1854Met (ACG>ATG): c.5561 C>T in exon 38 of the MYH7 gene (NM_000257.2). The Thr1854Met mutation in the MYH7 gene was reported in one individual diagnosed with HCM and not present in 400 normal chromosomes of African American and Caucasian backgrounds. (Of note, due to an error in the Van Driest et al. cited report, the mutation is denoted T1834M) (Van Driest S et al., 2004). In addition, Thr1854Met was identified in three individuals diagnosed with HCM from one family, two of whom were also heterozygous for a variant in the MYBPC3 gene (IVS14-13 G>A) (Page S et al., 2012). Furthermore, Thr1854Met was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Thr1854Met results in a non-conservative amino acid substitution of a hydrophilic, basic Threonine residue with a hydrophobic Methionine. Mutations in nearby residues (Lys1848Thr, Arg1858Met, Arg1863Gln) have been reported in association with cardiomyopathy, further supporting the functional importance of this region of the protein. The variant is found in HCM panel(s).