Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001383407 | SCV001582541 | pathogenic | Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 | 2020-06-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 43 of the PITX2 protein (p.Arg43Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This missense change is located in a region of the PITX2 protein where a significant number of previously reported PITX2 missense mutations are found (PMID: 20881294, 22224469). These observations suggest that this may be a clinically significant region of the protein. This variant has been reported to affect PITX2 protein function (PMID: 19218601). This variant has been observed in individual(s) with Axenfeld-Rieger syndrome (ARS) (PMID: 16389592, Invitae). It has also been observed to segregate with disease in related individuals. |
Revvity Omics, |
RCV001780324 | SCV002024638 | likely pathogenic | not provided | 2021-02-15 | criteria provided, single submitter | clinical testing |