ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2046G>T (p.Lys682Asn) (rs756493732)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000260355 SCV000417418 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV000476547 SCV000551886 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2016-07-04 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 682 of the SCN2A protein (p.Lys682Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs756493732, ExAC 0.006%) but has not been reported in the literature in individuals with a SCN2A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000713070 SCV000843637 uncertain significance not provided 2017-09-15 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000260355 SCV001428679 uncertain significance Benign familial neonatal-infantile seizures 2020-01-22 criteria provided, single submitter clinical testing

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