ClinVar Miner

Submissions for variant NM_001199138.2(NLRC4):c.1333T>C (p.Ser445Pro)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002469924 SCV002765885 likely pathogenic not provided 2022-12-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32537258, 34672126, 34248956, 27203668)
Labcorp Genetics (formerly Invitae), Labcorp RCV005227784 SCV005862805 pathogenic Periodic fever-infantile enterocolitis-autoinflammatory syndrome; Familial cold autoinflammatory syndrome 4 2024-11-30 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 445 of the NLRC4 protein (p.Ser445Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with NLRC4-related conditions (PMID: 27203668, 36797819). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1804623). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NLRC4 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NLRC4 function (PMID: 36797819). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.