ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.350C>G (p.Pro117Arg)

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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 RCV002651846 SCV003525863 pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2022-10-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro64 amino acid residue in PITX2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12381896, 16936096). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with clinical features of Axenfeld-Rieger syndrome (PMID: 16936096, 33304895; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 64 of the PITX2 protein (p.Pro64Arg).

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