ClinVar Miner

Submissions for variant NM_004895.5(NLRP3):c.911T>G (p.Phe304Cys)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039313 SCV001202839 pathogenic Cryopyrin associated periodic syndrome 2019-12-29 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with cysteine at codon 304 of the NLRP3 protein (p.Phe304Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of neonatal onset multisystemic inflammatory disease (Invitae). In at least one individual the variant was observed to be de novo. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Phe304 amino acid residue in NLRP3. Other variant(s) that disrupt this residue (also known as p.Phe302 in the literature) have been determined to be pathogenic (PMID: 22279087). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.