Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493699 | SCV000583180 | likely pathogenic | not provided | 2015-09-24 | criteria provided, single submitter | clinical testing | The I711V variant that is likely disease-causing in the STAT3 gene has been previously reported in association with primary immunodeficiency (Moens et al., 2014). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. I711V 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. However, in-silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Another missense change at the same residue (I711T) and missense variant in nearby residues (A703T, Y705N/C, L706M, T708S/N, K709E, F710C, V713M/L, T714A/I, T716M) have been reported in the Human Gene Mutation Database in association with STAT3-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003139697 | SCV003806836 | likely pathogenic | Hyper-IgE recurrent infection syndrome 1, autosomal dominant | 2022-06-09 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4 supporting, PM2 moderated, PM5 moderated, PP2 supporting, PP3 supporting |