Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158791 | SCV000208726 | pathogenic | not provided | 2014-08-25 | criteria provided, single submitter | clinical testing | p.Thr412Ser (ACC>TCC): c.1234 A>T in exon 13 of the MYH7 gene (NM_000257.2). The T412S variant that is likely pathogenic was identified in the MYH7 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. T412S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, the T412S variant 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (R403W, R403L, R403Q, V404M, V404L, V406M, G407V, V411I, Q418K) have been reported in association with HCM, supporting the functional importance of this region of the protein. Additionally, a missense mutation at the same residue (T412N) has been reported in a 40-year-old male with a clinical diagnosis of DCM, however, segregation studies were not performed (Villard et al., 2005). 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-CRDM panel(s). |