Submissions for variant NM_001370466.1(NOD2):c.417A>T (p.Glu139Asp)

gnomAD frequency: 0.00004  dbSNP: rs749605438

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002555831	SCV001229397	uncertain significance	Blau syndrome; Regional enteritis	2024-01-12	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 166 of the NOD2 protein (p.Glu166Asp). This variant is present in population databases (rs749605438, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with NOD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 858593). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001311447	SCV001501617	uncertain significance	not provided	2021-01-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001311447	SCV001716261	uncertain significance	not provided	2021-03-30	criteria provided, single submitter	clinical testing