Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000221733 | SCV000279192 | uncertain significance | not provided | 2014-03-04 | criteria provided, single submitter | clinical testing | The L96P variant has been reported previously, using alternate nomenclature, in a family with features of TRAPS, including fevers, abdominal pain, and urticaria (Dode et al., 2002). The L96P variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (N94I, H95L/Y) have been reported in the Human Gene Mutation Database in association with TNFRSF1A-related disorders (Stenson et al., 2009), supporting the functional importance of this region of the protein. The L96P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is moderately conserved across species. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. |
| Unité médicale des maladies autoinflammatoires, |
RCV000083937 | SCV000116049 | not provided | TNF receptor-associated periodic fever syndrome (TRAPS) | no assertion provided | not provided |