Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001383639 | SCV001582859 | pathogenic | DiGeorge syndrome | 2020-03-05 | criteria provided, single submitter | clinical testing | This variant disrupts the C-terminus of the TBX1 protein. Other variant(s) that disrupt this region (p.Ser408Trpfs*52) have been determined to be pathogenic (PMID: 14585638, 15703190). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TBX1-related conditions. 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 sequence change results in a premature translational stop signal in the TBX1 gene (p.Leu364Cysfs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 132 amino acids of the TBX1 protein. For these reasons, this variant has been classified as Pathogenic. |