ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1718G>A (p.Arg573His) (rs575162600)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000762594 SCV000892927 likely benign not provided 2018-09-30 criteria provided, single submitter clinical testing
GeneDx RCV000486401 SCV000565097 likely benign not specified 2017-09-08 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 RCV000650640 SCV000772487 uncertain significance Early infantile epileptic encephalopathy 14; Epilepsy, nocturnal frontal lobe, 5 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 573 of the KCNT1 protein (p.Arg573His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs575162600, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with KCNT1-related disease. ClinVar contains an entry for this variant (Variation ID: 418274). 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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