Submissions for variant NM_139276.3(STAT3):c.2153G>A (p.Cys718Tyr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002995267	SCV003295316	uncertain significance	Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function	2022-01-11	criteria provided, single submitter	clinical testing	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 cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 718 of the STAT3 protein (p.Cys718Tyr). 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. 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.
PreventionGenetics, part of Exact Sciences	RCV003395556	SCV004112149	uncertain significance	STAT3-related disorder	2023-07-07	criteria provided, single submitter	clinical testing	The STAT3 c.2153G>A variant is predicted to result in the amino acid substitution p.Cys718Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), 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.