ClinVar

Description

The Arg204Leu variant in MYH7 has not been reported in the literature, but has b een identified by our laboratory in 4 Caucasian individuals with HCM, one of who m also carried another variant of unknown significance in MYBPC3. This variant h as not been identified in large European American and African American populatio ns by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS); oth er populations have not been examined adequately. Arginine (Arg) at this positio n is conserved in mammals and chickens, but this part of the MYH7 protein appear s to be less well conserved in more distantly related species. In addition, this variant was predicted to be benign using a computational tool clinically valida ted by our laboratory. This tool's benign prediction is estimated to be correct 89% of the time (Jordan 2011). While the presence in multiple affected individua ls and absence from the general population are consistent with a role in disease , the computational data suggest that the variant may not impact the normal func tion of the protein. In summary, additional information is needed to fully asses s the clinical significance of the Arg204Leu variant.