Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000706399 | SCV000835446 | uncertain significance | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2018-01-09 | criteria provided, single submitter | clinical testing | Other missense substitutions at this codon (p.Ser636Phe and p.Ser636Tyr) have been reported in individuals affected with hyper IgE syndrome (PMID: 18602572, 20159255). This sequence change replaces serine with proline at codon 636 of the STAT3 protein (p.Ser636Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with STAT3-related disease. This variant is not present in population databases (ExAC no frequency). |