Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000083943 | SCV002239485 | pathogenic | TNF receptor-associated periodic fever syndrome (TRAPS) | 2022-07-12 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with tumor necrosis factor receptor-associated periodic syndrome (TRAPS) (PMID: 31562507). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 102 of the TNFRSF1A protein (p.Cys102Trp). This variant is also known as C73W. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys102 amino acid residue in TNFRSF1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15228183, 22343913, 24251727; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 TNFRSF1A protein function. ClinVar contains an entry for this variant (Variation ID: 97690). |
| Unité médicale des maladies autoinflammatoires, |
RCV000083943 | SCV000116056 | not provided | TNF receptor-associated periodic fever syndrome (TRAPS) | no assertion provided | not provided |