Submissions for variant NM_139276.3(STAT3):c.779T>C (p.Leu260Pro)

dbSNP: rs1598422720

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000810893	SCV000951130	uncertain significance	Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function	2019-06-27	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with proline at codon 260 of the STAT3 protein (p.Leu260Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with STAT3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
CeGaT Center for Human Genetics Tuebingen	RCV000996548	SCV001151310	uncertain significance	not provided	2018-08-01	criteria provided, single submitter	clinical testing