Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002547378 | SCV001532110 | uncertain significance | Blau syndrome; Regional enteritis | 2022-09-12 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NOD2 protein function. ClinVar contains an entry for this variant (Variation ID: 1035561). This variant has not been reported in the literature in individuals affected with NOD2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 487 of the NOD2 protein (p.Val487Ile). 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, |
RCV002261344 | SCV002542658 | uncertain significance | Autoinflammatory syndrome | 2018-02-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002546844 | SCV003738403 | uncertain significance | Inborn genetic diseases | 2022-11-03 | criteria provided, single submitter | clinical testing | The c.1459G>A (p.V487I) alteration is located in exon 4 (coding exon 4) of the NOD2 gene. This alteration results from a G to A substitution at nucleotide position 1459, causing the valine (V) at amino acid position 487 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |