ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2809C>T (p.Arg937Cys)

dbSNP: rs796053197
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, 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).
GenomeConnect - Simons Searchlight 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.

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