Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700281 | SCV000829029 | pathogenic | Axenfeld-Rieger syndrome type 3 | 2020-04-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Different truncations (p.Gln120*, Leu240Valfs*65, p.Ser320Argfs*81) that lie downstream of this variant have been determined to be pathogenic (PMID: 20881294, 16638984, 18498376, 11782474, Invitae). This suggests that deletion of this region of the FOXC1 protein is causative of disease. Experimental studies have shown that this nonsense change decreases FOXC1 stability, but increases its transcriptional activation activity (PMID: 25786029). This variant has been reported in an individual affected with congenital glaucoma and her mother, who had juvenile open-angle glaucoma (PMID: 25786029). ClinVar contains an entry for this variant (Variation ID: 100687). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the FOXC1 gene (p.Tyr47*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 503 amino acids of the FOXC1 protein. |
Human Genetics School of Medicine of Albacete, |
RCV000190252 | SCV000119898 | pathogenic | not provided | no assertion criteria provided | not provided | Converted during submission to Pathogenic. |