Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482070 | SCV000565631 | likely pathogenic | not provided | 2014-05-13 | criteria provided, single submitter | clinical testing | A novel E97Q variant that is likely pathogenic was identified in the TPM1 gene. It has not been published as a pathogenic variant or as a benign polymorphism to our knowledge. The E97Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The E97Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is highly conserved across species. Moreover, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function, however at least two models predict this variant is probably damaging to the protein structure.function. Furthermore, missense variants in nearby residues (I92T, V95A, A107T) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2009), supporting the functional importance of this region of the protein. Therefore, this is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |