ClinVar Miner

Submissions for variant NM_001065.4(TNFRSF1A):c.121G>C (p.Asp41His)

gnomAD frequency: 0.00002  dbSNP: rs199882512
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000658632 SCV000780414 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001376777 SCV001573941 likely pathogenic TNF receptor-associated periodic fever syndrome (TRAPS) 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 41 of the TNFRSF1A protein (p.Asp41His). This variant is present in population databases (rs199882512, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TNFRSF1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 546694). 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 disrupts the p.Asp41 amino acid residue in TNFRSF1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23322460). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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