ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.1309G>T (p.Gly437Trp)

dbSNP: rs104895492
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002513870 SCV000946181 uncertain significance Blau syndrome; Regional enteritis 2023-08-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 464 of the NOD2 protein (p.Gly464Trp). This variant is present in population databases (rs104895492, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with atypical Blau syndrome with Takayasu-like arteritis and cardiomyopathy (PMID: 22859352, 25416713). ClinVar contains an entry for this variant (Variation ID: 97829). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NOD2 protein function. Experimental studies have shown that this missense change affects NOD2 function (PMID: 25093298). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262678 SCV002543029 uncertain significance Autoinflammatory syndrome 2020-11-06 criteria provided, single submitter clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084085 SCV000116214 not provided Blau syndrome 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.