Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001885949 | SCV002138197 | uncertain significance | Severe combined immunodeficiency due to IKK2 deficiency | 2021-06-18 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IKBKB protein function. This variant has not been reported in the literature in individuals with IKBKB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 193 of the IKBKB protein (p.Leu193Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. |