Total submissions: 3
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, |
RCV002262678 | SCV002543029 | uncertain significance | Autoinflammatory syndrome | 2020-11-06 | criteria provided, single submitter | clinical testing | |
Unité médicale des maladies autoinflammatoires, |
RCV000084085 | SCV000116214 | not provided | Blau syndrome | no assertion provided | not provided |