ClinVar Miner

Submissions for variant NM_016123.4(IRAK4):c.376C>T (p.Pro126Ser)

gnomAD frequency: 0.00001  dbSNP: rs1379851408
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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 RCV000700088 SCV000828828 uncertain significance Immunodeficiency 67 2020-08-14 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IRAK4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This sequence change replaces proline with serine at codon 126 of the IRAK4 protein (p.Pro126Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine.
GenomeConnect - Invitae Patient Insights Network RCV000700088 SCV001749877 not provided Immunodeficiency 67 no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 08-13-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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