This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 694 of the STAT3 protein (p.His694Gln). This variant is present in population databases (rs139701269, gnomAD 0.01%). This missense change has been observed in individual(s) with leukocytosis and splenomegaly (PMID: 29296824). ClinVar contains an entry for this variant (Variation ID: 633187). 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.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Conflicting interpretations of pathogenicity
Uncertain significance(2); Likely benign(1)
- Review status:
- criteria provided, conflicting interpretations
- Submissions:
- 3
- First in ClinVar:
- Jun 3, 2019
- Most recent Submission:
- May 16, 2022
- Last evaluated:
- Dec 8, 2021
- Accession:
- VCV000633187.8
- Variation ID:
- 633187
- Description:
- single nucleotide variant
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NM_139276.3(STAT3):c.2082T>A (p.His694Gln)
- Allele ID
- 621567
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17q21.2
- Genomic location
- 17: 42322301 (GRCh38) GRCh38 UCSC
- 17: 40474319 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_139276.3:c.2082T>A MANE Select NP_644805.1:p.His694Gln missense NM_001369512.1:c.2082T>A NP_001356441.1:p.His694Gln missense NM_001369513.1:c.2082T>A NP_001356442.1:p.His694Gln missense NM_001369514.1:c.2082T>A NP_001356443.1:p.His694Gln missense NM_001369516.1:c.2082T>A NP_001356445.1:p.His694Gln missense NM_001369517.1:c.2082T>A NP_001356446.1:p.His694Gln missense NM_001369518.1:c.2082T>A NP_001356447.1:p.His694Gln missense NM_001369519.1:c.2082T>A NP_001356448.1:p.His694Gln missense NM_001369520.1:c.2082T>A NP_001356449.1:p.His694Gln missense NM_001384984.1:c.1998T>A NP_001371913.1:p.His666Gln missense NM_001384985.1:c.2004T>A NP_001371914.1:p.His668Gln missense NM_001384986.1:c.2097T>A NP_001371915.1:p.His699Gln missense NM_001384987.1:c.2061T>A NP_001371916.1:p.His687Gln missense NM_001384988.1:c.2082T>A NP_001371917.1:p.His694Gln missense NM_001384989.1:c.1986T>A NP_001371918.1:p.His662Gln missense NM_001384990.1:c.2097T>A NP_001371919.1:p.His699Gln missense NM_001384991.1:c.2055T>A NP_001371920.1:p.His685Gln missense NM_001384992.1:c.2022T>A NP_001371921.1:p.His674Gln missense NM_001384993.1:c.2082T>A NP_001371922.1:p.His694Gln missense NM_003150.4:c.2082T>A NP_003141.2:p.His694Gln missense NM_213662.2:c.2082T>A NP_998827.1:p.His694Gln missense NC_000017.11:g.42322301A>T NC_000017.10:g.40474319A>T NG_007370.1:g.71195T>A LRG_112:g.71195T>A LRG_112t1:c.2082T>A LRG_112p1:p.His694Gln - Protein change
- H694Q, H668Q, H674Q, H685Q, H687Q, H699Q, H662Q, H666Q
- Other names
- -
- Canonical SPDI
- NC_000017.11:42322300:A:T
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- The Genome Aggregation Database (gnomAD), exomes 0.00008
- The Genome Aggregation Database (gnomAD) 0.00011
- Exome Aggregation Consortium (ExAC) 0.00007
- Trans-Omics for Precision Medicine (TOPMed) 0.00012
- NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- The Genome Aggregation Database (gnomAD) 0.00019
- Links
- dbSNP: rs139701269
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 1 | criteria provided, single submitter | Dec 8, 2021 | RCV001070774.4 | |
| Conflicting interpretations of pathogenicity | 2 | criteria provided, conflicting interpretations | Feb 17, 2020 | RCV000781324.5 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Jun 07, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919270.1
First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019 |
|
|
|
Likely benign
(Feb 17, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory,University of Chicago
Accession: SCV002066309.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Uncertain significance
(Dec 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
STAT3 gain of function
Hyper-IgE recurrent infection syndrome 1
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001236042.3
First in ClinVar: Apr 15, 2020 Last updated: May 16, 2022 |
Comment:
This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 694 of the STAT3 protein (p.His694Gln). … (more)
This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 694 of the STAT3 protein (p.His694Gln). This variant is present in population databases (rs139701269, gnomAD 0.01%). This missense change has been observed in individual(s) with leukocytosis and splenomegaly (PMID: 29296824). ClinVar contains an entry for this variant (Variation ID: 633187). 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. (less)
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Systematic STAT3 sequencing in patients with unexplained cytopenias identifies unsuspected large granular lymphocytic leukemia. | Morgan EA | Blood advances | 2017 | PMID: 29296824 |
Text-mined citations for rs139701269...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Jun 24, 2022