Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001938453 | SCV002195630 | uncertain significance | Neutropenia, severe congenital, 2, autosomal dominant | 2020-12-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with GFI1-related conditions. This sequence change replaces threonine with isoleucine at codon 391 of the GFI1 protein (p.Thr391Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |