ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.833T>C (p.Ile278Thr) (rs1057523728)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494098 SCV000581717 likely pathogenic not provided 2015-02-10 criteria provided, single submitter clinical testing A novel I278T variant that is likely pathogenic has been identified in the KCNQ2 gene. The I278T variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The I278T 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 alters a conserved position predicted to be within the pore-forming loop between the S5 and S6 transmembrane segments of the KCNQ2 protein, and multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with KCNQ2-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000585874 SCV000693807 likely pathogenic Early infantile epileptic encephalopathy 7 2018-01-01 criteria provided, single submitter clinical testing

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