Submissions for variant NM_012452.2(TNFRSF13B):c.58C>T (p.Arg20Cys) (rs200013015)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000700484	SCV000829241	uncertain significance	Common variable immunodeficiency 2	2019-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 20 of the TNFRSF13B protein (p.Arg20Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs200013015, ExAC 0.01%). This variant has been observed in an individual affected with hyper-IgM syndrome or common variable immunodeficiency (PMID: 20652909). This variant has also been reported in an individual affected with systemic lupus erythematosus (SLE) (PMID: 17464555). However, this variant was absent in this individual's son, who was also affected with SLE, which suggests that this variant was not likely a primary cause of disease in this family. ClinVar contains an entry for this variant (Variation ID: 577672). 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 tolerated, 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.
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles	RCV000735375	SCV000854529	uncertain significance	Seizures; Micrognathia; Cognitive impairment; Cafe-au-lait spot; Frontal bossing; High forehead; Abnormality of the basal ganglia; Thoracic scoliosis; Abnormal basal ganglia MRI signal intensity		criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV001171924	SCV001334827	uncertain significance	not provided	2020-03-01	criteria provided, single submitter	clinical testing

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