Submissions for variant NM_012452.2(TNFRSF13B):c.512T>G (p.Leu171Arg) (rs143027621)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000506368	SCV000605393	pathogenic	not specified	2017-01-03	criteria provided, single submitter	clinical testing
Invitae	RCV000648134	SCV000769948	uncertain significance	Common variable immunodeficiency 2	2019-11-29	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with arginine at codon 171 of the TNFRSF13B protein (p.Leu171Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is present in population databases (rs143027621, ExAC 0.03%). This variant has been reported as homozygous, compound heterozygous, and heterozygous in individuals and families affected with common variable immunodeficiency (PMID: 17983875, 17392798, 19779048, 22697072, 23237420). It has also been observed as heterozygous in asymptomatic individuals from these same families (PMID: 23237420, 22697072). ClinVar contains an entry for this variant (Variation ID: 440340). Experimental studies have shown that this missense change impairs the expression and function of the TACI protein (PMID: 21419480). 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 Praxis fuer Humangenetik Tuebingen	RCV000762232	SCV000892514	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000762232	SCV000928296	uncertain significance	not provided	2019-03-22	criteria provided, single submitter	clinical testing