ClinVar Miner

Submissions for variant NM_004895.4(NLRP3):c.3043A>G (p.Lys1015Glu) (rs771315000)

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 RCV000222974 SCV000278966 uncertain significance not provided 2014-02-02 criteria provided, single submitter clinical testing To our knowledge, the K1015E missense substitution has neither been published as a mutation, nor reported as a benign polymorphism. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. K1015E represents a non-conservative amino acid substitution as a positively-charged Lysine residue is replaced with a negatively-charged Glutamic Acid residue. However, this substitution occurs at a position in the NLRP3 protein that is only moderately conserved among species and is not located in the NACHT/NBD domain, which is the domain where the vast majority of NLRP3 disease-associated mutations have been identified. Therefore, based on the currently available information, it is unclear whether K1015E is a disease-causing mutation or a rare benign variant.
Invitae RCV000690719 SCV000818419 uncertain significance Cryopyrin associated periodic syndrome 2018-02-28 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 1015 of the NLRP3 protein (p.Lys1015Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs771315000, ExAC 0.001%). This variant has not been reported in the literature in individuals with NLRP3-related disease. ClinVar contains an entry for this variant (Variation ID: 234308). 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.