ClinVar Miner

Submissions for variant NM_001370466.1(NOD2):c.1240G>A (p.Glu414Lys) (rs104895432)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638048 SCV000759528 uncertain significance Blau syndrome; Inflammatory bowel disease 1 2019-11-09 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 441 of the NOD2 protein (p.Glu441Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs104895432, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in individuals affected with Crohn's disease (PMID: 11875755, 15024686). ClinVar contains an entry for this variant (Variation ID: 97827). Experimental studies have shown that this missense change does not significantly affect basal or peptidoglycan-induced NFkB activity compared to wildtype protein (PMID: 12626759) and does not affect interaction with CARD9 (PMID: 24960071). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658746 SCV000780535 uncertain significance not provided 2018-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001119854 SCV001278304 uncertain significance Inflammatory bowel disease 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000084082 SCV001278305 benign Blau syndrome 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084082 SCV000116211 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.