ClinVar Miner

Submissions for variant NM_001323289.2(CDKL5):c.1892T>C (p.Ile631Thr) (rs144878564)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725189 SCV000334780 uncertain significance not provided 2015-09-09 criteria provided, single submitter clinical testing
GeneDx RCV000133333 SCV000729863 likely benign not specified 2017-07-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659290 SCV000781094 uncertain significance Early infantile epileptic encephalopathy 2 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000700107 SCV000828848 uncertain significance Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 631 of the CDKL5 protein (p.Ile631Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs144878564, ExAC 0.02%). This variant has been observed in an individual affected with seizures who also had a pathogenic variant in CDKL5 (PMID: 19793311). ClinVar contains an entry for this variant (Variation ID: 143786). 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 tolerated, but 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.
RettBASE RCV000133333 SCV000188342 likely benign not specified 2014-05-09 no assertion criteria provided curation Identified in unaffect female with random X-inactivation pattern; in silico predictions: SIFT = tolerated, MutationTaster = polymorphism, PolyPhen2 = benign, AlignGVGD = benign (C0)

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