Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002562593 | SCV001396669 | uncertain significance | Blau syndrome; Regional enteritis | 2023-01-03 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Crohn disease (PMID: 16278823). This variant is present in population databases (rs104895491, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1019 of the NOD2 protein (p.Arg1019Gly). ClinVar contains an entry for this variant (Variation ID: 952371). 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. Experimental studies have shown that this missense change does not substantially affect NOD2 function (PMID: 15998797, 16804397). 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. |