Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000813719 | SCV000954089 | uncertain significance | Combined immunodeficiency due to OX40 deficiency | 2020-03-04 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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. This variant has not been reported in the literature in individuals with TNFRSF4-related conditions. This variant is present in population databases (rs776572462, ExAC 0.04%). This sequence change replaces proline with serine at codon 202 of the TNFRSF4 protein (p.Pro202Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV004028798 | SCV004967922 | uncertain significance | not specified | 2023-12-22 | criteria provided, single submitter | clinical testing | The c.604C>T (p.P202S) alteration is located in exon 5 (coding exon 5) of the TNFRSF4 gene. This alteration results from a C to T substitution at nucleotide position 604, causing the proline (P) at amino acid position 202 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |