ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1885A>G (p.Lys629Glu) (rs1057522978)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425973 SCV000530238 likely pathogenic not provided 2016-10-04 criteria provided, single submitter clinical testing The K629E variant in the KCNT1 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different substitution at the same codon, K629N, has been previously reported as a de novo pathogenic variant in an individual with neonatal seizures and functional studies have demonstrated gain of function (Mikati et al., 2015). The K629E variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K629E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Testing of this individual's parents indicates this variant is apparently de novo in this individual. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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