ClinVar Miner

Submissions for variant NM_016123.4(IRAK4):c.1371G>A (p.Met457Ile)

gnomAD frequency: 0.00003  dbSNP: rs766606181
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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 RCV000806419 SCV000946416 uncertain significance Immunodeficiency 67 2023-08-30 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 651127). This variant has not been reported in the literature in individuals affected with IRAK4-related conditions. This variant is present in population databases (rs766606181, gnomAD 0.003%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 457 of the IRAK4 protein (p.Met457Ile).
Ambry Genetics RCV004028243 SCV004890822 uncertain significance Inborn genetic diseases 2023-12-09 criteria provided, single submitter clinical testing The c.1371G>A (p.M457I) alteration is located in exon 12 (coding exon 11) of the IRAK4 gene. This alteration results from a G to A substitution at nucleotide position 1371, causing the methionine (M) at amino acid position 457 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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