Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000231604 | SCV000284296 | pathogenic | Hypertrophic cardiomyopathy | 2016-11-23 | criteria provided, single submitter | clinical testing | Family studies have indicated that this variant was not present in the parents of an individual with hypertrophic cardiomyopathy, which suggests that it was de novo in that affected individual (Invitae). This sequence change replaces alanine with glutamic acid at codon 254 of the MYH7 protein (p.Ala254Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH7-related disease. For these reasons, this variant has been classified as Pathogenic. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). |