Description
The C59R missense variant in the TNFRSF1A gene has been reported previously, as C30R, in association with TRAPS (McDermott et al., 1999). C59R was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This non-conservative amino acid substitution occurs at a conserved position in a cysteine-rich domain of the extracellular region of the TNFRSF1A protein. Loss of this cysteine residue is expected to disrupt disulfide bond formation, resulting in improper protein folding and abnormal localization of the protein in the cell (Lobito et al., 2006). Missense variants in the same (C59F/Y/S) and nearby residues (C58R/Y/F, C62G/Y) have been reported in the Human Gene Mutation Database in association with TRAPS (Stenson et al., 2014). Therefore, we interpret C59R as a pathogenic variant.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
