Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001946260 | SCV002216247 | uncertain significance | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2021-05-08 | 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, 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 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 asparagine with serine at codon 481 of the STAT3 protein (p.Asn481Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |
Prevention |
RCV004754812 | SCV005354328 | uncertain significance | STAT3-related disorder | 2024-09-13 | no assertion criteria provided | clinical testing | The STAT3 c.1442A>G variant is predicted to result in the amino acid substitution p.Asn481Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |