ClinVar Miner

Submissions for variant NM_139276.3(STAT3):c.2116C>A (p.Leu706Met)

dbSNP: rs2144622987
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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 RCV001967161 SCV002198201 pathogenic Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 706 of the STAT3 protein (p.Leu706Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hyper IgE syndrome (PMID: 20048285). ClinVar contains an entry for this variant (Variation ID: 1429110). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change affects STAT3 function (PMID: 27315770). This variant disrupts the p.Leu706 amino acid residue in STAT3. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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