ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.649A>G (p.Thr217Ala)

dbSNP: rs1057516089
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001294297 SCV001483169 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-04-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Thr217 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23621294). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KCNQ2 function (PMID: 16319223). 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: 369757). This missense change has been observed in individual(s) with benign familial neonatal-infantile seizures (PMID: 23360469). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 217 of the KCNQ2 protein (p.Thr217Ala).
GeneReviews RCV000678134 SCV000484572 not provided Seizures, benign familial neonatal, 1 no assertion provided literature only BFIS (benign familial infantile seizures)

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