Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Johns Hopkins Genomics, |
RCV001254616 | SCV001430634 | likely pathogenic | STAT3-related early-onset multisystem autoimmune disease | 2020-06-04 | criteria provided, single submitter | clinical testing | This STAT3 variant is absent from a large population dataset and has an entry in ClinVar. It has been reported in two unrelated patients with autosomal dominant infantile-onset multisystem autoimmune disease-1. Independent functional studies have shown that the p.Lys658Asn substitution confers hypersensitivity to interleukins resulting in persistent activation of STAT3 signaling in vitro. This variant is not predicted to affect normal exon 21 splicing, although this has not been confirmed experimentally to our knowledge. We consider c.1974G>T to be likely pathogenic. |