ClinVar

Description

Variant summary: The MYH7 c.3777C>T (p.His1259His) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 23/121404 control chromosomes (1 homozygote), predominantly observed in the African subpopulation at a frequency of 0.002114 (22/10406). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic MYH7 variant (0.0012508), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign and one lab classified it as VUS, all without evidence for independent evaluaiton. Taken together, this variant is classified as likely benign.