ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.522C>G (p.Tyr174Ter)

dbSNP: rs951710742
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001989873 SCV002236038 pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2020-12-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr121*) in the PITX2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 151 amino acid(s) 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: 17167399). 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.
Human Developmental Genetics Laboratory, Medical College of Wisconsin RCV002290812 SCV002538935 pathogenic Axenfeld-Rieger syndrome type 1 2022-06-23 criteria provided, single submitter research
MGZ Medical Genetics Center RCV002290812 SCV002581017 likely pathogenic Axenfeld-Rieger syndrome type 1 2022-08-30 criteria provided, single submitter clinical testing

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