ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.2T>A (p.Met1Lys) (rs118192186)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000594914 SCV000702341 likely pathogenic not provided 2016-11-11 criteria provided, single submitter clinical testing
Invitae RCV000809476 SCV000949628 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2018-12-02 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the KCNQ2 mRNA. The next in-frame methionine is located at codon 174. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. Disruption of the initiator codon has been observed to segregate with familial neonatal seizures in several families (PMID: 14985406, 25982755, Invitae). ClinVar contains an entry for this variant (Variation ID: 497690). Experimental studies have not been reported for this initiator codon variant and its effect on protein expression is unknown. However, a missense variant located upstream of the next in-frame methionine (p.Arg144Gln) has been determined to be pathogenic (PMID: 23934111, 25740509). This suggests that even if translation is rescued by an in-frame methionine, deletion of the N-terminal region of the KCNQ2 protein is likely to be deleterious. For these reasons, this variant has been classified as Pathogenic.

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