Submissions for variant NM_012452.3(TNFRSF13B):c.418G>A (p.Glu140Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001035270	SCV001198593	uncertain significance	Common variable immunodeficiency 2	2019-03-12	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with lysine at codon 140 of the TNFRSF13B protein (p.Glu140Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs199578237, ExAC 0.02%). This variant has been observed in individuals affected with common variable immunodeficiency (CVID) (PMID: 19779048, 22884984). 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.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001035270	SCV001429112	uncertain significance	Common variable immunodeficiency 2	2017-12-13	criteria provided, single submitter	clinical testing