Submissions for variant NM_139276.3(STAT3):c.974G>A (p.Arg325Gln)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002632042	SCV002974582	uncertain significance	Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function	2022-06-21	criteria provided, single submitter	clinical testing	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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 affected with STAT3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 325 of the STAT3 protein (p.Arg325Gln).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003992676	SCV004810191	uncertain significance	Hyper-IgE recurrent infection syndrome 1, autosomal dominant	2024-04-04	criteria provided, single submitter	clinical testing