Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004226143 | SCV003743950 | uncertain significance | not specified | 2022-11-23 | criteria provided, single submitter | clinical testing | The c.510C>A (p.D170E) alteration is located in exon 5 (coding exon 5) of the TNFRSF4 gene. This alteration results from a C to A substitution at nucleotide position 510, causing the aspartic acid (D) at amino acid position 170 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003745550 | SCV004453495 | uncertain significance | Combined immunodeficiency due to OX40 deficiency | 2023-06-04 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 2394592). This variant has not been reported in the literature in individuals affected with TNFRSF4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 170 of the TNFRSF4 protein (p.Asp170Glu). |