ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1394C>T (p.Thr465Met) (rs539139475)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720408 SCV000851285 likely benign Seizures 2017-06-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724047 SCV000226157 uncertain significance not provided 2014-09-04 criteria provided, single submitter clinical testing
GeneDx RCV000174790 SCV000535873 likely benign not specified 2017-01-17 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.
Invitae RCV000804237 SCV000944134 uncertain significance Early infantile epileptic encephalopathy 14; Epilepsy, nocturnal frontal lobe, 5 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 465 of the KCNT1 protein (p.Thr465Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs539139475, ExAC 0.04%). This variant has not been reported in the literature in individuals with KCNT1-related disease. ClinVar contains an entry for this variant (Variation ID: 194424). 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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