Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002016656 | SCV002306376 | uncertain significance | Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 | 2021-08-05 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Axenfeld-Rieger syndrome (PMID: 30457409; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 73 of the PITX2 protein (p.Ala73Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. 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. 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. |