ClinVar Miner

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

dbSNP: rs1057523728
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494098 SCV000581717 pathogenic not provided 2021-12-02 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30109124, 31780880, 27602407)
NeuroMeGen, Hospital Clinico Santiago de Compostela RCV000585874 SCV000693807 likely pathogenic Developmental and epileptic encephalopathy, 7 2018-01-01 criteria provided, single submitter clinical testing
Invitae RCV002527074 SCV003462416 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-03-23 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ile278 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 429212). This missense change has been observed in individual(s) with clinical features of KCNQ2-related conditions (PMID: 30109124). In at least one individual the variant was observed to be de novo. This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 278 of the KCNQ2 protein (p.Ile278Thr).
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV003444106 SCV004042682 likely pathogenic KCNQ2-Related Disorders criteria provided, single submitter clinical testing
Channelopathy-Associated Epilepsy Research Center RCV003315347 SCV004015083 not provided Complex neurodevelopmental disorder no assertion provided literature only

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