Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002514477 | SCV001486772 | uncertain significance | Blau syndrome; Regional enteritis | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 612 of the NOD2 protein (p.Ala612Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs104895439, ExAC 0.003%). This missense change has been observed in individual(s) with Crohn's disease (PMID: 11385576, 11875755). This variant is also known as A585V. ClinVar contains an entry for this variant (Variation ID: 97841). 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: 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. |
Unité médicale des maladies autoinflammatoires, |
RCV000084098 | SCV000116229 | not provided | Blau syndrome | no assertion provided | not provided |