Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189235 | SCV000242867 | pathogenic | not provided | 2017-04-12 | criteria provided, single submitter | clinical testing | The R937C missense mutation was previously identified as a de novo variant in an individual with intellectual disability (Raunch et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R937C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution alters a highly conserved residue in the predicted pore loop, between transmembrane domains 5 and 6, of the second homologous repeat domain. The variant is found in EPILEPSY panel(s). |
Fulgent Genetics, |
RCV000763455 | SCV000894231 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000763455 | SCV004569561 | pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-03-08 | 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 937 of the SCN2A protein (p.Arg937Cys). For these reasons, this variant has been classified as Pathogenic. 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 SCN2A protein function. ClinVar contains an entry for this variant (Variation ID: 207080). This missense change has been observed in individual(s) with clinical features of SCN2A-related conditions (PMID: 23020937, 28256214, 29655203, 31332282, 31957018). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). |
Genome |
RCV001265271 | SCV001443388 | pathogenic | Complex neurodevelopmental disorder | 2018-07-02 | no assertion criteria provided | provider interpretation | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-07-02 and interpreted as Pathogenic. Variant was initially reported on 2018-03-19 by GTR ID of laboratory name 500105. The reporting laboratory might also submit to ClinVar. |