ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.1061C>T (p.Ala354Val) (rs121908149)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091235 SCV001247145 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing
Invitae RCV001225906 SCV001398200 likely pathogenic Cryopyrin associated periodic syndrome 2019-08-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 354 of the NLRP3 protein (p.Ala354Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Muckle-Wells syndrome in a family and has been reported in unrelated individuals affected with cryopyrin-associated periodic syndrome (PMID: 11687797, 30431487, 21109514, 29047407). This variant is also known as p.Ala352Val in the literature. ClinVar contains an entry for this variant (Variation ID: 4373). This variant has been reported to affect NLRP3 protein function (PMID: 19501000, 29322034). This variant disrupts the p.Ala354 amino acid residue in NLRP3. Other variant(s) that disrupt this residue have been observed in individuals with NLRP3-related conditions (PMID: 26931528), which suggests that this may be a clinically significant amino acid residue. 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.
OMIM RCV000004621 SCV000024795 pathogenic Familial amyloid nephropathy with urticaria AND deafness 2001-11-01 no assertion criteria provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084171 SCV000116302 not provided Familial cold urticaria no assertion provided not provided

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.