Submissions for variant NM_001065.4(TNFRSF1A):c.349T>G (p.Cys117Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002601704	SCV002949898	likely pathogenic	TNF receptor-associated periodic fever syndrome (TRAPS)	2022-04-08	criteria provided, single submitter	clinical testing	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. This missense change has been observed in individual(s) with clinical features of TNF receptor-associated periodic fever syndrome (PMID: 32248184). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 117 of the TNFRSF1A protein (p.Cys117Gly). 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. This variant disrupts the p.Cys117 amino acid residue in TNFRSF1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9529351, 10199409). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.