ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.2617G>A (p.Ala873Thr) (rs201867582)

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 RCV000217829 SCV000278962 uncertain significance not provided 2013-08-05 criteria provided, single submitter clinical testing To our knowledge, the A873T missense substitution has neither been published as a mutation, nor as a benign polymorphism. A873T represents a semi-conservative substitution between two uncharged amino acids as a non-polar Alanine residue is replaced with a polar Threonine residue at a position that is not well conserved. The NHLBI ESP Exome Variant Server reports that A873T was not observed at any significant frequency in individuals of African American or European backgrounds, indicating it is not a common benign variant in these populations. Therefore, the clinical significance of A873T is unclear at this time
Invitae RCV000698307 SCV000826967 uncertain significance Cryopyrin associated periodic syndrome 2018-05-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 873 of the NLRP3 protein (p.Ala873Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs201867582, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with NLRP3-related disease. ClinVar contains an entry for this variant (Variation ID: 234304). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.