ClinVar

Description

p.Glu401Lys: c.1201 G>A. The E401K mutation in the DES gene has been reported previously in one individual with cardiomyopathy and muscle weakness as a de novo mutation (Goudeau et al., 2006). E401K results in a non-conservative amino acid substitution in the C-terminal end of the 2B helical segment at a position that is conserved across species (Goudeau B et al., 2006;). In addition, functional studies have shown that the E401K mutation results in dysfunctinal desmin filament assembly (Goudeau B et al., 2006; Chourbagi O et al., 2010). Moreover, mutations in nearby residues (L392P, N393I, D399Y, R406W) have been reported in association with desmin related myopathy, further supporting the functional importance of this region of the protein. Furthermore, the E401K mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, E401K in the DES gene is interpreted as a disease-causing mutation The variant is found in DES panel(s).