ClinVar Miner

Submissions for variant NM_016123.4(IRAK4):c.1124T>C (p.Val375Ala)

gnomAD frequency: 0.00002  dbSNP: rs779773825
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001367960 SCV001564333 uncertain significance Immunodeficiency 67 2021-08-11 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 375 of the IRAK4 protein (p.Val375Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs779773825, ExAC 0.09%). This variant has not been reported in the literature in individuals with IRAK4-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").
Ambry Genetics RCV003298599 SCV004006729 uncertain significance Inborn genetic diseases 2023-03-24 criteria provided, single submitter clinical testing The c.1124T>C (p.V375A) alteration is located in exon 9 (coding exon 8) of the IRAK4 gene. This alteration results from a T to C substitution at nucleotide position 1124, causing the valine (V) at amino acid position 375 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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