ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.700_716dup (p.Thr239_Gly240insCysProGlnGlnTer)

dbSNP: rs2110431524
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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 RCV001942226 SCV002232607 pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2021-11-04 criteria provided, single submitter clinical testing This variant disrupts a region of the PITX2 protein in which other variant(s) (p.Val211Argfs*29) have been determined to be pathogenic (PMID: 31529555). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with PITX2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly187Cysfs*5) in the PITX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 85 amino acid(s) of the PITX2 protein. For these reasons, this variant has been classified as Pathogenic.

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