Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000187875 | SCV000231221 | likely pathogenic | not provided | 2014-10-22 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000187875 | SCV000241475 | pathogenic | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23692823, 28133863, 28867141, 29056246, 28191890, 24318194, 27779742, 25533962, 28135719, 27535030, 33084218, 31957018, 31785789, 33811133, 31440721, 34992632, 27602407) |
Genetic Services Laboratory, |
RCV000192955 | SCV000247667 | likely pathogenic | Seizure | 2014-06-03 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000555510 | SCV000634076 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 265 of the KCNQ2 protein (p.Ala265Thr). This variant is present in population databases (rs794727740, gnomAD 0.0009%). This missense change has been observed in individual(s) with early onset epileptic encephalopathy (PMID: 23692823, 27535030, 27602407, 27779742). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 197891). 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. This variant disrupts the p.Ala265 amino acid residue in KCNQ2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22275249, 22926866). 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. |
Ce |
RCV000187875 | SCV001247386 | pathogenic | not provided | 2018-07-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000187875 | SCV001448017 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV000179032 | SCV003921969 | pathogenic | Developmental and epileptic encephalopathy, 7 | 2020-11-05 | criteria provided, single submitter | clinical testing | 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with early infantile epileptic encephalopathy 7 (MIM#613720) (PMID: 24318194). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to threonine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0701 - Other missense variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Two different variants in the same codon resulting in changes to a valine and proline have been previously reported as pathogenic in patients with early infantile epileptic encephalopathy (ClinVar, PMID: 31552204). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been previously reported as pathogenic in patients with early infantile epileptic encephalopathy (ClinVar, PMID: 29056246, PMID: 27535030). (SP) 1102 - Strong phenotype match for this individual. (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Neuro |
RCV000179032 | SCV000258972 | pathogenic | Developmental and epileptic encephalopathy, 7 | no assertion criteria provided | clinical testing | ||
Gene |
RCV000179032 | SCV000484577 | not provided | Developmental and epileptic encephalopathy, 7 | no assertion provided | literature only | EE (epileptic encephalopathy) |