ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.3149C>T (p.Thr1050Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001270711 SCV001451456 uncertain significance Epilepsy, nocturnal frontal lobe, 5 2019-06-17 criteria provided, single submitter clinical testing The KCNT1 c.3149C>T (p.Thr1050Ile) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The p.Thr1050Ile variant is reported at a frequency of 0.000009 in the European (Non-Finnish) population of the Genome Aggregation Database though this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the limited evidence, the p.Thr1050Ile variant is classified as a variant of uncertain significance for KCNT1-realted epilepsy.
Invitae RCV001362103 SCV001558105 uncertain significance Early infantile epileptic encephalopathy 14; Epilepsy, nocturnal frontal lobe, 5 2020-02-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1050 of the KCNT1 protein (p.Thr1050Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KCNT1-related conditions. 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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