Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001377970 | SCV001575431 | likely pathogenic | Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 | 2020-08-20 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 4-5 of the PITX2 gene. The 5' boundary is likely confined to intron 3. 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. This variant has not been reported in the literature in individuals with PITX2-related conditions. This variant disrupts the OAR or aristaless domain which mediates the interaction with a number of proteins that are required for PITX2 transcriptional transactivation activity (PMID: 10490637, 18045789, 15728254). While functional studies have not been performed to directly test the effect of this variant on PITX2 protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |