Submissions for variant NM_003327.4(TNFRSF4):c.631G>A (p.Gly211Arg)

gnomAD frequency: 0.00010  dbSNP: rs757565777

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001222055	SCV001394136	uncertain significance	Combined immunodeficiency due to OX40 deficiency	2023-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 211 of the TNFRSF4 protein (p.Gly211Arg). This variant is present in population databases (rs757565777, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TNFRSF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 950362). 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 TNFRSF4 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.
CeGaT Center for Human Genetics Tuebingen	RCV003405408	SCV004126896	uncertain significance	not provided	2023-02-01	criteria provided, single submitter	clinical testing	TNFRSF4: PM2, BP4