Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001378695 | SCV001576321 | likely pathogenic | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2020-09-08 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 been observed in individual(s) with hyper IgE syndrome (PMID: 18591412, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 642 of the STAT3 protein (p.Lys642Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |