Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002903522 | SCV003252169 | uncertain significance | Severe combined immunodeficiency due to IKK2 deficiency | 2024-06-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 364 of the IKBKB protein (p.Asp364Asn). This variant is present in population databases (rs760398648, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with IKBKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 2044219). 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 IKBKB 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. |
| Ambry Genetics | RCV002903521 | SCV003703613 | uncertain significance | Inborn genetic diseases | 2022-11-10 | criteria provided, single submitter | clinical testing | The c.1090G>A (p.D364N) alteration is located in exon 11 (coding exon 10) of the IKBKB gene. This alteration results from a G to A substitution at nucleotide position 1090, causing the aspartic acid (D) at amino acid position 364 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |