Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001348178 | SCV001542470 | uncertain significance | Immunodeficiency 67 | 2022-07-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 69 of the IRAK4 protein (p.Glu69Ala). This variant is present in population databases (rs202134282, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with IRAK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043990). 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 expected to disrupt IRAK4 protein function. 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 | RCV004036545 | SCV004890823 | uncertain significance | Inborn genetic diseases | 2023-09-23 | criteria provided, single submitter | clinical testing | The c.206A>C (p.E69A) alteration is located in exon 3 (coding exon 2) of the IRAK4 gene. This alteration results from a A to C substitution at nucleotide position 206, causing the glutamic acid (E) at amino acid position 69 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |