Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000189137 | SCV000242769 | uncertain significance | not provided | 2015-11-16 | criteria provided, single submitter | clinical testing | p.Glu1162Val (GAG>GTG): c.3485 A>T in exon 18 of the SCN2A gene (NM_021007.2). The Glu1162Val missense change in SCN2A has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project did not report Glu1162Val with a relevant allele frequency in approximately 5,000 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. Glu1162Val is a non-conservative substitution since a negatively charged Glutamic acid residue is replaced by a neutral, non-polar Valine residue. This substitution alters a highly conserved position in the intracellular loop between the second and third transmembrane domains of the protein, and different mutations in this loop have been published in association with benign familial neonatal-infantile seizures (BFNIS) and intractable childhood epilepsy (Shi et al., 2011). Multiple in silico algorithms predict that Glu1162Val is damaging to protein structure/function, although another classifies it as a likely benign change. Therefore, based on the currently available information, it is unclear whether Glu1162Val is a disease-causing mutation or a rare benign variant.The variant is found in CHILD-EPI panel(s). |
| Invitae | RCV000795173 | SCV000934617 | likely benign | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-08-23 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV002288794 | SCV002580282 | uncertain significance | Episodic ataxia, type 9 | 2021-10-20 | criteria provided, single submitter | clinical testing |