Description
p.Leu1428Ser (TTG>TCG): c.4283 T>C in exon 31 of the MYH7 gene (NM_000257.2). A missense variant that is likely pathogenic was identified in the MYH7 gene. It has not been published as a mutation or been reported as a benign polymorphism to our knowledge, however it has been identified in other unrelated individuals tested at GeneDx. The L1428S variant was not observed 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. The L1428S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, the L1428 residue, located in the myosin heavy chain, is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Lastly, Missense mutations in nearby residues (R1420W, R1420Q, E1426K, R1434C) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in DCM,HCM panel(s).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
