Submissions for variant NM_016123.4(IRAK4):c.447C>G (p.Asp149Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002690778	SCV002990214	uncertain significance	Immunodeficiency 67	2022-03-01	criteria provided, single submitter	clinical testing	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 IRAK4 protein function. This variant has not been reported in the literature in individuals affected with IRAK4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 149 of the IRAK4 protein (p.Asp149Glu).
Ambry Genetics	RCV003375676	SCV004095624	uncertain significance	Inborn genetic diseases	2023-08-15	criteria provided, single submitter	clinical testing	The c.447C>G (p.D149E) alteration is located in exon 4 (coding exon 3) of the IRAK4 gene. This alteration results from a C to G substitution at nucleotide position 447, causing the aspartic acid (D) at amino acid position 149 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.