ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1712G>A (p.Arg571His) (rs138138150)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189217 SCV000242849 uncertain significance not specified 2013-05-29 criteria provided, single submitter clinical testing p.Arg571His (CGC>CAC): c.1712 G>A in exon 12 of the SCN2A gene (NM_021007.2). The Arg571His missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. Arg571His is a conservative change as both Arginine and Histidine are positively charged, polar amino acids. It alters a highly conserved position in the intracellular loop between the first and second transmembrane domain of the protein. In silico algorithms are not consistent in their predictions as to whether or not Arg571His is damaging to the structure/function of the SCN2A protein. Therefore, based on the currently available information, it is unclear whether Arg571His is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae RCV000691494 SCV000819277 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2019-11-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 571 of the SCN2A protein (p.Arg571His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs138138150, 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 autism (PMID: 30564305). This variant is also known as g.166179706 in the literature. ClinVar contains an entry for this variant (Variation ID: 207062). 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: "Probably Damaging"; 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 RCV000691494 SCV000895294 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2018-10-31 criteria provided, single submitter clinical testing

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