ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1976G>A (p.Gly659Asp) (rs368887417)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766774 SCV000242856 uncertain significance not provided 2017-01-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN2A gene. The G659D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G659D variant is observed in 16/61,030 (0.03%) alleles from individuals of Eurpoean background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G659D 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 in the cytoplasmic loop between the first and second homologous domains. Furthermore, 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.
Illumina Clinical Services Laboratory,Illumina RCV000391073 SCV000417412 benign Benign familial neonatal-infantile seizures 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV001086292 SCV000551880 likely benign Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000189224 SCV000615055 likely benign not specified 2017-07-03 criteria provided, single submitter clinical testing

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