ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.1741C>T (p.Arg581Ter)

gnomAD frequency: 0.00001  dbSNP: rs118192236
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187920 SCV000241522 pathogenic not provided 2019-09-03 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 14534157, 25525159, 25982755, 26993267, 31199083)
Invitae RCV000636351 SCV000757790 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-11-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg581*) in the KCNQ2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ2 are known to be pathogenic (PMID: 14534157, 23692823, 27779742). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with benign familial neonatal seizures (PMID: 14534157, 25982755, 26993267). ClinVar contains an entry for this variant (Variation ID: 21768). For these reasons, this variant has been classified as Pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000678061 SCV001980686 pathogenic Seizures, benign familial neonatal, 1 2020-07-11 criteria provided, single submitter clinical testing This nonsense variant found in exon 15 of 17 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a heterozygous change in families with benign familial neonatal seizures (PMID: 14534157, 31199083, 26993267, 25982755). It is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.1741C>T (p.Arg581Ter) variant is classified as Pathogenic.
Revvity Omics, Revvity RCV000187920 SCV003826515 pathogenic not provided 2022-01-07 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV003335050 SCV004046328 pathogenic KCNQ2-Related Disorders criteria provided, single submitter clinical testing This nonsense variant found in exon 15 of 17 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a heterozygous change, predominantly inherited from an affected parent but also as a de novo change, in individuals with neonatal seizures (PMID: 14534157, 31199083, 26993267, 25982755, 19380078, 32863083, 34153113). It is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the maternal sample was negative for the c.1741C>T (p.Arg581Ter) variant. Based on the available evidence, the c.1741C>T (p.Arg581Ter) variant is classified as Pathogenic.
GeneReviews RCV000678061 SCV000041620 not provided Seizures, benign familial neonatal, 1 no assertion provided literature only BFNE (benign familial neonatal epilepsy)
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV000678061 SCV001752421 pathogenic Seizures, benign familial neonatal, 1 no assertion criteria provided clinical testing
GenomeConnect - Invitae Patient Insights Network RCV003335050 SCV004228791 not provided KCNQ2-Related Disorders no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 01-31-2021 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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