Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV003150890 | SCV003839073 | uncertain significance | STAT3-related early-onset multisystem autoimmune disease | 2023-01-23 | criteria provided, single submitter | clinical testing | This STAT3 missense variant (rs776115471) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 2/251376 total alleles; 0.0008%; no homozygotes). It has not been reported in ClinVar nor the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be deleterious, but these algorithms have low specificity, especially for predicting gain of function or dominant negative variants. The arginine residue at this position is evolutionarily conserved across most of the species assessed. We consider the clinical significance of c.1004G>A;p.Arg335Gln in STAT3 to be uncertain at this time. |
Johns Hopkins Genomics, |
RCV003150889 | SCV003839074 | uncertain significance | Hyper-IgE recurrent infection syndrome 1, autosomal dominant | 2023-01-23 | criteria provided, single submitter | clinical testing | This STAT3 missense variant (rs776115471) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 2/251376 total alleles; 0.0008%; no homozygotes). It has not been reported in ClinVar nor the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be deleterious, but these algorithms have low specificity, especially for predicting gain of function or dominant negative variants. The arginine residue at this position is evolutionarily conserved across most of the species assessed. We consider the clinical significance of c.1004G>A;p.Arg335Gln in STAT3 to be uncertain at this time. |