Submissions for variant NM_139276.3(STAT3):c.2228G>T (p.Gly743Val)

gnomAD frequency: 0.00011  dbSNP: rs151033214

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001719019	SCV000725687	likely benign	not provided	2019-01-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000707338	SCV000836430	likely benign	Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function	2025-01-26	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768099	SCV000899001	uncertain significance	Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3-related early-onset multisystem autoimmune disease	2021-03-30	criteria provided, single submitter	clinical testing	STAT3 NM_139276.2 exon 23 p.Gly743Val (c.2228G>T): This variant has not been reported in the literature but is present in 34/126596 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs151033214). This variant is present in ClinVar (Variation ID:514074). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV001719019	SCV004698799	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	STAT3: PP2, BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV001719019	SCV005412715	uncertain significance	not provided	2024-05-30	criteria provided, single submitter	clinical testing	PP2, PS3_supporting
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV005231171	SCV005872167	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935696	SCV004765643	uncertain significance	STAT3-related disorder	2024-01-12	no assertion criteria provided	clinical testing	The STAT3 c.2228G>T variant is predicted to result in the amino acid substitution p.Gly743Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.