ClinVar Miner

Submissions for variant NM_139276.3(STAT3):c.1915C>G (p.Pro639Ala)

dbSNP: rs2144683531
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001950022 SCV002205362 pathogenic Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function 2021-08-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro639 amino acid residue in STAT3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17881745, 20159255, 26743515, 27884935). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 missense change has been observed in individuals with STAT3-related conditions (PMID: 17881745; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 639 of the STAT3 protein (p.Pro639Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine.

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