Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001982154 | SCV002209789 | uncertain significance | Combined immunodeficiency due to OX40 deficiency | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 55 of the TNFRSF4 protein (p.Arg55Cys). This variant is present in population databases (rs769325973, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. 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: 1433024). 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 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. |
| Ambry Genetics | RCV004042078 | SCV004967915 | uncertain significance | not specified | 2023-12-15 | criteria provided, single submitter | clinical testing | The c.163C>T (p.R55C) alteration is located in exon 2 (coding exon 2) of the TNFRSF4 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |