Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489515 | SCV000576936 | likely pathogenic | not provided | 2017-04-14 | criteria provided, single submitter | clinical testing | The D292E variant in the STAT1 gene has been reported in a 10-year-old male from a cohort of patients with chronic mucocutaneous candidiasis, without additional phenotypic details (Toubiana et al., 2016). The D292E variant was reported by the authors to be a gain of function variant, but the data was not shown. A different variant of the same amino acid, D292N, was reported in a 21-year-old female in the same study (Toubiana et al., 2016). The D292E variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D292E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret D292E as a likely pathogenic variant. |
| Labcorp Genetics |
RCV000795005 | SCV000934443 | likely pathogenic | Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency | 2018-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 292 of the STAT1 protein (p.Asp292Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with chronic mucocutaneous candidiasis (PMID: 27114460). ClinVar contains an entry for this variant (Variation ID: 426484). Experimental studies have reported that this missense acts as a gain-of-function variant, however, the data was not shown (PMID: 27114460). This variant disrupts the p.Asp292 amino acid residue in STAT1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 27114460), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Mendelics | RCV000986960 | SCV001136123 | likely pathogenic | Immunodeficiency 31B | 2019-05-28 | criteria provided, single submitter | clinical testing |