Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000802571 | SCV000942408 | pathogenic | Anophthalmia-microphthalmia syndrome | 2019-03-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. In addition, a different truncation (p.Gln97*) that lies downstream of this variant has been reported in individuals with coloboma or anophthalmia/microphthalmia, and determined to be pathogenic (PMID: 24033328, 24167467, 18781617). This variant disrupts the Otx tails within the C-terminal domain (amino acids 247-289), which are responsible for the transactivation activity of the OTX2 protein (PMID: 16607563). While functional studies have not been performed to directly test the effect of this variant on OTX2 protein function, this suggests that disruption of this region of the protein is causative of disease. This variant has not been reported in the literature in individuals with a OTX2-related disease. This variant is a gross deletion of the genomic region encompassing exons 2-3 of the OTX2 gene. The 5' boundary is likely confined to intron 1. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. |