Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000083923 | SCV000941847 | uncertain significance | TNF receptor-associated periodic fever syndrome (TRAPS) | 2018-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tryptophan at codon 81 of the TNFRSF1A protein (p.Cys81Trp). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Infevers database (PMID: 12520003). ClinVar contains an entry for this variant (Variation ID: 97670). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys81 amino acid residue (also known as p.Cys52) in TNFRSF1A. Other variant(s) that disrupt this residue have been observed in individuals with TNFRSF1A-related conditions (PMID: 13130484, 16508982, 10199409), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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. |
| Unité médicale des maladies autoinflammatoires, |
RCV000083923 | SCV000116035 | not provided | TNF receptor-associated periodic fever syndrome (TRAPS) | no assertion provided | not provided |