Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001887102 | SCV002157682 | uncertain significance | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2023-01-26 | 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. 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 not expected to disrupt STAT3 protein function. ClinVar contains an entry for this variant (Variation ID: 1389278). This variant has not been reported in the literature in individuals affected with STAT3-related conditions. This variant is present in population databases (rs371953916, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 338 of the STAT3 protein (p.Val338Ile). |
Ambry Genetics | RCV002554134 | SCV003538776 | uncertain significance | Inborn genetic diseases | 2022-11-17 | criteria provided, single submitter | clinical testing | The c.1012G>A (p.V338I) alteration is located in exon 10 (coding exon 9) of the STAT3 gene. This alteration results from a G to A substitution at nucleotide position 1012, causing the valine (V) at amino acid position 338 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |