ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.361dup (p.Thr121fs)

dbSNP: rs1553922891
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543429 SCV000653742 likely pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2017-07-06 criteria provided, single submitter clinical testing 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, 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. This variant has not been reported in the literature in individuals with PITX2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the PITX2 gene (p.Thr68Asnfs*131). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 204 amino acids of the PITX2 protein.

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