Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001383808 | SCV001583076 | pathogenic | Axenfeld-Rieger syndrome type 3 | 2020-08-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change results in a premature translational stop signal in the FOXC1 gene (p.Tyr18Thrfs*27). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 536 amino acids of the FOXC1 protein. 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 has not been reported in the literature in individuals with FOXC1-related conditions. This variant disrupts the C-terminus of the FOXC1 protein. Other variant(s) that disrupt this region (p.Ala381Glyfs*147) have been determined to be pathogenic (PMID: 20881294, 16936096, 11170889). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. |