Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000702887 | SCV000831760 | uncertain significance | Severe combined immunodeficiency due to IKK2 deficiency | 2023-08-05 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with IKBKB-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 aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 174 of the IKBKB protein (p.Asp174Glu). ClinVar contains an entry for this variant (Variation ID: 579568). 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. 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. |
| Ambry Genetics | RCV002533670 | SCV003562347 | uncertain significance | Inborn genetic diseases | 2021-07-09 | criteria provided, single submitter | clinical testing | The c.522T>G (p.D174E) alteration is located in exon 7 (coding exon 6) of the IKBKB gene. This alteration results from a T to G substitution at nucleotide position 522, causing the aspartic acid (D) at amino acid position 174 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |