Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001378195 | SCV001575706 | likely pathogenic | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2020-10-24 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Met394 amino acid residue in STAT3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28579554). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STAT3 protein function. This variant has not been reported in the literature in individuals with STAT3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 394 of the STAT3 protein (p.Met394Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. |