ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.515del (p.Gln172fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Developmental Genetics Laboratory, Medical College of Wisconsin RCV002293558 SCV002538934 pathogenic Axenfeld-Rieger syndrome type 1 2022-06-23 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV003774801 SCV004569791 pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2023-08-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln119Argfs*36) in the PITX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 153 amino acid(s) of the PITX2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Axenfeld–Rieger Syndrome (PMID: 29506241, 31185933). This variant is also known as c.515delA (p.Gln172ArgfsX36). ClinVar contains an entry for this variant (Variation ID: 1693123). This variant disrupts a region of the PITX2 protein in which other variant(s) (p.Trp133*) have been determined to be pathogenic (PMID: 8944018, 16498627). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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