ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4940G>A (p.Arg1647His)

dbSNP: rs797044927
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190766 SCV000244207 uncertain significance Inborn genetic diseases 2013-07-15 criteria provided, single submitter clinical testing There is insufficient or conflicting evidence for classification of this alteration.
Labcorp Genetics (formerly Invitae), Labcorp RCV002514088 SCV003260814 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-08-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1647 of the SCN2A protein (p.Arg1647His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 208746). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN2A protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV004797793 SCV005419532 likely pathogenic not provided 2024-05-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the C-terminal cytoplasmic domain between the S4 and S5 transmembrane segments of the fourth homologous domain.; This variant is associated with the following publications: (PMID: 29466837)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.