ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1038C>A (p.Phe346Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001219954 SCV001391921 likely pathogenic Early infantile epileptic encephalopathy 14; Epilepsy, nocturnal frontal lobe, 5 2019-07-02 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 346 of the KCNT1 protein (p.Phe346Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with early infantile epileptic encephalopathy (PMID: 29390993, 30868116, 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 tolerated, 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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