ClinVar Miner

Submissions for variant NM_012452.2(TNFRSF13B):c.236A>G (p.Tyr79Cys) (rs72553876)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000327211 SCV000605398 likely pathogenic not specified 2017-04-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723608 SCV000331382 uncertain significance not provided 2015-11-19 criteria provided, single submitter clinical testing
Invitae RCV000648139 SCV000769953 uncertain significance Common variable immunodeficiency 2 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 79 of the TNFRSF13B protein (p.Tyr79Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs72553876, ExAC 0.06%). This variant has been reported in compound heterozygosity in individuals affected with IgG subclass deficiency and in a healthy heterozygote from one family (PMID: 18981294). This variant does not appear to segregate with disease in this family. It has also been reported in an individual affected with with common variable immunodeficiency (CVID) and an individual affected with primary hypo/dysgammaglobulinemia (PMID: 22884984). ClinVar contains an entry for this variant (Variation ID: 281110). Experimental studies have shown that this missense change results in decreased protein expression, abolished ligand binding, and absent NFκB/NFAT signaling (PMID: 21419480, 21458042, 18954329). 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.

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