Submissions for variant NM_001556.3(IKBKB):c.1200G>C (p.Gln400His)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002760972	SCV003012691	uncertain significance	Severe combined immunodeficiency due to IKK2 deficiency	2022-10-02	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 400 of the IKBKB protein (p.Gln400His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IKBKB-related conditions. 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. 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.
PreventionGenetics, part of Exact Sciences	RCV003418603	SCV004106787	uncertain significance	IKBKB-related disorder	2023-05-16	criteria provided, single submitter	clinical testing	The IKBKB c.1200G>C variant is predicted to result in the amino acid substitution p.Gln400His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.