Submissions for variant NM_001040142.2(SCN2A):c.5752C>T (p.Arg1918Cys) (rs139899756)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000509344	SCV000334115	uncertain significance	not provided	2015-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000509344	SCV000617025	uncertain significance	not provided	2016-11-17	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the SCN2A gene. The R1918C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1918C variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in an external variant database. The R1918C 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. This substitution alters a conserved residue predicted to be within the C-terminal cytoplasmic domain, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with SCN2A-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics	RCV000718780	SCV000849644	likely benign	History of neurodevelopmental disorder	2019-05-06	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Other strong data supporting benign classification
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000509344	SCV001152497	uncertain significance	not provided	2018-05-01	criteria provided, single submitter	clinical testing
Invitae	RCV001034485	SCV001197842	likely benign	Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11	2019-08-07	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000509344	SCV000607254	not provided	not provided		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.