ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1229C>T (p.Pro410Leu)

gnomAD frequency: 0.00001  dbSNP: rs752579642
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000530666 SCV000634040 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2024-01-11 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 410 of the KCNQ2 protein (p.Pro410Leu). 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 variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 461403). 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 with a negative predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KCNQ2 function (PMID: 35104249). 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000660441 SCV000782533 uncertain significance Seizures, benign familial neonatal, 1; Developmental and epileptic encephalopathy, 7 2016-11-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001311999 SCV001502407 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing KCNQ2: PP2, BS1:Supporting
Channelopathy-Associated Epilepsy Research Center RCV003315352 SCV004015049 not provided Complex neurodevelopmental disorder no assertion provided literature only

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