ClinVar Miner

Submissions for variant NM_139276.3(STAT3):c.986T>G (p.Met329Arg)

dbSNP: rs1555566820
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV001027631 SCV001190203 uncertain significance Inherited Immunodeficiency Diseases 2019-01-01 criteria provided, single submitter research
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV001805975 SCV002053785 likely pathogenic STAT3-related early-onset multisystem autoimmune disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002552425 SCV003472616 likely pathogenic Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function 2022-09-13 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Met329 amino acid residue in STAT3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33365035, 33717144). 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. ClinVar contains an entry for this variant (Variation ID: 827744). This missense change has been observed in individual(s) with STAT3-related conditions (PMID: 30443250, 32499645). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 329 of the STAT3 protein (p.Met329Arg).

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