Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000803541 | SCV000943419 | pathogenic | TWIST1-related craniosynostosis; Saethre-Chotzen syndrome | 2018-09-06 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the TWIST1 gene (p.Ser93Lysfs*145). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 110 amino acids of the TWIST1 protein and extend the protein by an additional 35 amino acids. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with TWIST1-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant results in an extension of the TWIST1 protein. Other variant(s) that result in a similarly extended protein product (p.Thr137Hisfs*101) have been determined to be pathogenic (24127277, Invitae). This suggests that these extensions are likely to be causative of disease. |