ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3457G>A (p.Glu1153Lys) (rs200138205)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189136 SCV000242768 likely benign not specified 2017-05-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory,University of Chicago RCV000189136 SCV000248813 benign not specified 2017-11-28 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725887 SCV000340256 uncertain significance not provided 2016-03-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000302248 SCV000417436 likely benign Benign familial neonatal-infantile seizures 2018-01-13 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 RCV000463410 SCV000551887 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2019-09-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1153 of the SCN2A protein (p.Glu1153Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs200138205, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with Rolandic epilepsy (PMID: 29358611). ClinVar contains an entry for this variant (Variation ID: 206987). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000463410 SCV000611520 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2017-05-23 criteria provided, single submitter clinical testing
Bioinformatics Core,Luxembourg Center for Systems Biomedicine RCV000655981 SCV000588257 pathogenic Rolandic epilepsy 2017-01-01 no assertion criteria provided case-control CAADphred>15

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