Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002014040 | SCV002303771 | likely pathogenic | Congenital myopathy 4B, autosomal recessive; Congenital myopathy with fiber type disproportion | 2021-10-11 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asp15 amino acid residue in TPM3. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TPM3 protein function. This variant has not been reported in the literature in individuals affected with TPM3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with valine at codon 15 of the TPM3 protein (p.Asp15Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. |