ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.383G>A (p.Trp128Ter)

dbSNP: rs1729000976
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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 RCV001217543 SCV001389389 pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2019-07-06 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PITX2 gene (p.Trp75*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 197 amino acids of the PITX2 protein. This variant is not present in population databases (ExAC no frequency). This nonsense change has been observed in individual(s) with Axenfeld-Rieger syndrome (PMID: 20881294, 22569110). In at least one individual the variant was observed to be de novo. This variant disrupts the C-terminus of the PITX2 protein. Other variant(s) that disrupt this region (p.Trp133*) have been determined to be pathogenic (PMID: 8944018, 16498627). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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