ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1732A>G (p.Met578Val)

dbSNP: rs1057516123
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480958 SCV000569469 pathogenic not provided 2023-04-30 criteria provided, single submitter clinical testing This substitution is predicted to be within the C-terminal cytoplasmic domain.; Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); 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: 25982755, 20437616, 31418850, 35104249)
Invitae RCV001850942 SCV002293435 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-02-05 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 369807). This missense change has been observed in individual(s) with KCNQ2-related conditions (PMID: 25982755). It has also been observed to segregate with disease in related individuals. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 578 of the KCNQ2 protein (p.Met578Val).
GeneReviews RCV000678193 SCV000484642 not provided Seizures, benign familial neonatal, 1 no assertion provided literature only BFNE (benign familial neonatal epilepsy)
Channelopathy-Associated Epilepsy Research Center RCV003315343 SCV004015028 not provided Complex neurodevelopmental disorder no assertion provided literature only

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