Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002537445 | SCV000960363 | uncertain significance | Blau syndrome; Regional enteritis | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 760 of the NOD2 protein (p.Arg760Cys). This variant is present in population databases (rs3813758, gnomAD 0.005%). This missense change has been observed in individual(s) with Crohn’s disease (PMID: 16485124). ClinVar contains an entry for this variant (Variation ID: 662116). 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%. 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. |