Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001812547 | SCV002049169 | uncertain significance | not provided | 2021-02-10 | criteria provided, single submitter | clinical testing | The NOD2 c.2368C>T; p.Arg790Trp variant (rs62029861) is reported in the literature in an individual with inflammatory bowel disease (Schnitzler 2006), but to our knowledge, is not reported in an individual with a periodic fever disease. The variant is reported in the general population with an overall allele frequency of 0.008% (23/281,246 alleles) in the Genome Aggregation Database. The arginine at codon 790 is moderately conserved but computational analyses predict that this variant is neutral (REVEL: 0.129). Due to limited information, the clinical significance of the p.Arg790Trp variant is uncertain at this time. References: Schnitzler et al. Eight novel CARD15 variants detected by DNA sequence analysis of the CARD15 gene in 111 patients with inflammatory bowel disease. Immunogenetics. 2006 Apr;58(2-3):99-106. |
Genome Diagnostics Laboratory, |
RCV002261379 | SCV002542685 | uncertain significance | Autoinflammatory syndrome | 2019-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002542350 | SCV003516851 | uncertain significance | Blau syndrome; Regional enteritis | 2023-08-04 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Crohn’s disease (PMID: 16485124). 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. 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. ClinVar contains an entry for this variant (Variation ID: 1330980). This variant is present in population databases (rs62029861, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 790 of the NOD2 protein (p.Arg790Trp). |