ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.1613T>G (p.Ile538Arg) (rs1567139944)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698176 SCV000826822 uncertain significance Epileptic encephalopathy, childhood-onset 2018-03-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with arginine at codon 538 of the CHD2 protein (p.Ile538Arg). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHD2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000698176 SCV000898596 uncertain significance Epileptic encephalopathy, childhood-onset 2018-07-09 criteria provided, single submitter clinical testing CHD2 NM_001271.3 exon 14 p.Ile538Arg (c.1613T>G): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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