Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002514479 | SCV001538039 | uncertain significance | Blau syndrome; Regional enteritis | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 843 of the NOD2 protein (p.Glu843Lys). This variant is present in population databases (rs104895445, gnomAD 0.02%). This missense change has been observed in individual(s) with Crohn's disease (PMID: 11875755). ClinVar contains an entry for this variant (Variation ID: 97854). 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 with a negative predictive value of 95%. Experimental studies have shown that this missense change affects NOD2 function (PMID: 12626759). 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. |
Gene |
RCV001753486 | SCV001987703 | uncertain significance | not provided | 2020-06-05 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Reported in association with susceptibility to Crohn disease in one patient in published literature, but it is unknown if this individual was screened for variants in other genes associated with the phenotype (Lesage et al., 2002); This variant is associated with the following publications: (PMID: 11875755) |
Genome Diagnostics Laboratory, |
RCV002260982 | SCV002542699 | uncertain significance | Autoinflammatory syndrome | 2018-09-01 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001753486 | SCV003799594 | uncertain significance | not provided | 2022-04-01 | criteria provided, single submitter | clinical testing | The NOD2 c.2527G>A; p.Glu843Lys variant (rs104895445), is reported in the literature in an individual affected with Chron's disease (Lesage, 2002). This variant is found in the general population with an overall allele frequency of 0.008 % (23/282,748 alleles) in the Genome Aggregation Database. The glutamic acid at codon 843 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.19). Due to limited information, the clinical significance of the p.Glu843Lys variant is uncertain at this time. References: Lesage S et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet. 2002 Apr;70(4):845-57. PMID: 11875755. |
Unité médicale des maladies autoinflammatoires, |
RCV000084111 | SCV000116242 | not provided | Blau syndrome | no assertion provided | not provided |