ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.3424G>A (p.Glu1142Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720697 SCV000851577 likely benign History of neurodevelopmental disorder 2018-02-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Does not segregate with disease in family study (genes with incomplete penetrance)
Invitae RCV000791955 SCV000931226 uncertain significance Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1142 of the CACNA1A protein (p.Glu1142Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs780535727, ExAC 0.003%). This variant has not been reported in the literature in individuals with CACNA1A-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 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.

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