Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000623334 | SCV000741224 | pathogenic | Inborn genetic diseases | 2015-12-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001214076 | SCV001385739 | likely pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2020-03-11 | criteria provided, single submitter | clinical testing | This variant has been observed in individuals affected with autism spectrum disorder and seizures (PMID: 27824329, 28379373). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 520893). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ala1773 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 1773 of the SCN2A protein (p.Ala1773Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. |
Gene |
RCV002051868 | SCV002319076 | pathogenic | not provided | 2022-03-24 | criteria provided, single submitter | clinical testing | A different missense change at this residue (A1773T) has been reported as likely pathogenic in ClinVar and pathogenic in the published literature in association with SCN2A-related disorders (ClinVar SCV000551877.4; Miao et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); 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 substitution is predicted to be within the transmembrane segment S6 of the fourth homologous domain; This variant is associated with the following publications: (PMID: 32090326, 28379373, 31105003, 32400968, 27824329, 31785789) |
Genome |
RCV001265277 | SCV001443394 | pathogenic | Complex neurodevelopmental disorder | 2016-05-04 | no assertion criteria provided | provider interpretation | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2016-05-04 and interpreted as Pathogenic. Variant was initially reported on 2016-01-18 by GTR ID of laboratory name 61756. The reporting laboratory might also submit to ClinVar. |