Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187895 | SCV000241497 | pathogenic | not provided | 2020-12-23 | criteria provided, single submitter | clinical testing | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29726930) |
Athena Diagnostics | RCV000187895 | SCV000613874 | likely pathogenic | not provided | 2024-07-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with benign neonatal seizures and at least one individual with epileptic encephalopathy where it appears to occur de novo. Multiple affected individuals have been reported with missense changes at this codon, suggesting this variant also causes disease. Polyphen and MutationTaster predict this amino acid change may be damaging to the protein. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. |
Labcorp Genetics |
RCV000694219 | SCV000822653 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-06-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 353 of the KCNQ2 protein (p.Arg353Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of benign familial neonatal seizures (PMID: 29726930). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205898). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg353 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25959266). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Duke University Health System Sequencing Clinic, |
RCV003223393 | SCV003919016 | likely pathogenic | Seizures, benign familial neonatal, 1 | 2023-04-20 | criteria provided, single submitter | research |