ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1259C>T (p.Pro420Leu)

gnomAD frequency: 0.00004  dbSNP: rs139164500
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000278824 SCV000340929 uncertain significance not provided 2016-05-13 criteria provided, single submitter clinical testing
Invitae RCV000796621 SCV000936141 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 420 of the KCNQ2 protein (p.Pro420Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with early-onset epilepsy (PMID: 25959266). This variant is also known as p.Pro420Met. ClinVar contains an entry for this variant (Variation ID: 287222). 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 not expected to disrupt KCNQ2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002521968 SCV003679134 uncertain significance Inborn genetic diseases 2021-11-11 criteria provided, single submitter clinical testing Milh, 2015 Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneReviews RCV000678174 SCV000484619 not provided Developmental and epileptic encephalopathy, 7 no assertion provided literature only EE (epileptic encephalopathy)

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