ClinVar Miner

Submissions for variant NM_003159.2(CDKL5):c.2783C>T (p.Thr928Met) (rs951430019)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532113 SCV000639475 uncertain significance Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2017-01-23 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 928 of the CDKL5 protein (p.Thr928Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CDKL5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). The methionine 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. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000716870 SCV000847714 likely benign History of neurodevelopmental disorder 2016-08-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)

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