Submissions for variant NM_001330260.2(SCN8A):c.632T>G (p.Val211Gly)

dbSNP: rs1592380834

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001922799	SCV002171802	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2021-07-05	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val211 (p.Val9 in the literature) amino acid residue in SCN8A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30951195). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This missense change has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. This sequence change replaces valine with glycine at codon 211 of the SCN8A protein (p.Val211Gly). The SCN8A gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001330260.1, and corresponds to NM_014191.3:c.706+173T>G in the primary transcript.
GenomeConnect - Brain Gene Registry	RCV003987932	SCV004804576	not provided	Developmental and epileptic encephalopathy, 13; Seizures, benign familial infantile, 5; Myoclonus, familial, 2		no assertion provided	phenotyping only	Variant classified as Pathogenic and reported on 07-12-2021 by Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.