ClinVar Miner

Submissions for variant NM_000074.2(CD40LG):c.379A>G (p.Ile127Val) (rs1052924444)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788794 SCV000928040 uncertain significance not provided 2018-11-06 criteria provided, single submitter clinical testing
Invitae RCV000796869 SCV000936401 uncertain significance X-linked hyper-IgM syndrome 2018-09-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 127 of the CD40LG protein (p.Ile127Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CD40LG-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 valine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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