Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000083921 | SCV000958005 | likely pathogenic | TNF receptor-associated periodic fever syndrome (TRAPS) | 2018-07-24 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the p.Cys81 amino acid residue in TNFRSF1A have been observed in affected individuals (PMID: 10199409, 16508982). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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 has been observed to segregate with TNF receptor-associated periodic fever syndrome in a family (PMID: 13130484). ClinVar contains an entry for this variant (Variation ID: 97668). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 81 of the TNFRSF1A protein (p.Cys81Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. |
| Unité médicale des maladies autoinflammatoires, |
RCV000083921 | SCV000116032 | not provided | TNF receptor-associated periodic fever syndrome (TRAPS) | no assertion provided | not provided |