ClinVar Miner

Submissions for variant NM_001065.4(TNFRSF1A):c.172T>G (p.Cys58Gly)

dbSNP: rs2136823066
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002017706 SCV002306440 likely pathogenic TNF receptor-associated periodic fever syndrome (TRAPS) 2021-06-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 58 of the TNFRSF1A protein (p.Cys58Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. 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.Cys58 amino acid residue in TNFRSF1A. Other variant(s) that disrupt this residue (also known as p.Cys29) have been observed in individuals with TNFRSF1A-related conditions (PMID: 20532935, 19541728, 11700162), which suggests that this may be a clinically significant amino acid residue. 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 variant has not been reported in the literature in individuals with TNFRSF1A-related conditions. This variant is not present in population databases (ExAC no frequency).

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