Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479221 | SCV000569821 | likely pathogenic | not provided | 2021-09-20 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation as the last 371 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 14738421) |
| Victorian Clinical Genetics Services, |
RCV002272253 | SCV002557486 | pathogenic | Developmental and epileptic encephalopathy, 11 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with SCN2A-related disorders. Variants causing a gain of function result in either developmental and epileptic encephalopathy 11 (MIM#613721) or benign familial infantile seizures 3 (MIM#607745), whereas variants displaying a loss of function cause autism spectrum disorder and/or intellectual disability, with or without childhood-onset seizures; the functional consequence of truncating variants is unknown (OMIM, PMID: 29691040). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant is located within the final ion transport domain (NCBI, PDB). (I) 0701 - Other truncating variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. At least 8 other downstream truncating variants have previously been reported as pathogenic in individuals with SCN2A-related disorders (ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. The variant has previously been classified as likely pathogenic, however no further information was provided (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 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 |
| Revvity Omics, |
RCV000479221 | SCV003812595 | likely pathogenic | not provided | 2022-03-21 | criteria provided, single submitter | clinical testing |