Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000083917 | SCV002299417 | likely pathogenic | TNF receptor-associated periodic fever syndrome (TRAPS) | 2021-08-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 72 of the TNFRSF1A protein (p.Cys72Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This missense change has been observed in individuals with TNFRSF1A-related conditions (PMID: 23965844, 26598380; Invitae). 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. 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: 97664). This variant is also known as p.Cys43Tyr. |
| Unité médicale des maladies autoinflammatoires, |
RCV000083917 | SCV000116027 | not provided | TNF receptor-associated periodic fever syndrome (TRAPS) | no assertion provided | not provided |