ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1619T>G (p.Ile540Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001218484 SCV001390366 likely pathogenic Early infantile epileptic encephalopathy 2019-07-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with serine at codon 540 of the KCNQ2 protein (p.Ile540Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with clinical features of early infantile epileptic encephalopathy (Invitae). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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