Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000530817 | SCV000653741 | likely pathogenic | Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 | 2017-03-25 | criteria provided, single submitter | clinical testing | This variant is an in-frame deletion of the genomic region encompassing most of exons 4-5 of the PITX2 gene (c.71_760del, p.Glu26_Asn255del). While it preserves the integrity of the reading frame, it is expected to result in the loss of 229 amino acids (~84%) of the PITX2 protein. This deletion has not been reported in the literature in individuals with a PITX2-related disease. This variant is expected to disrupt the functionally conserved OAR or aristaless domain, which is located in the final 39 amino acids of the PITX2 protein. This domain mediates the interaction with a number of proteins that are required for PITX2 transcriptional transactivation activity (PMID: 10490637, 18045789, 15728254). In summary, this variant is a novel in frame deletion that is expected to delete most of the coding sequence and disrupt an important protein binding domain. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |