Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000179024 | SCV000231213 | uncertain significance | not provided | 2014-07-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001852224 | SCV002176248 | uncertain significance | Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 | 2021-10-02 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg91 amino acid residue in PITX2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29506241; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects PITX2 function (PMID: 24604414). 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. ClinVar contains an entry for this variant (Variation ID: 197883). This missense change has been observed in individual(s) with PITX2-related conditions and/or Rieger syndrome (PMID: 28611552; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 91 of the PITX2 protein (p.Arg91Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. |
| Human Developmental Genetics Laboratory, |
RCV002293425 | SCV002538951 | pathogenic | Axenfeld-Rieger syndrome type 1 | 2022-06-23 | criteria provided, single submitter | research |