ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5837A>G (p.Glu1946Gly) (rs121918802)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000416094 SCV000493672 uncertain significance not provided 2016-07-31 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764283 SCV000895302 uncertain significance Familial hemiplegic migraine type 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000416094 SCV000242655 uncertain significance not provided 2017-12-28 criteria provided, single submitter clinical testing The E1957G variant in the SCN1A gene has been reported previously in an individual with infantile spasms and mild intellectual disability; however, family studies were not performed (Wallace at al., 2003). The E1957G variant is observed in 27/126,186 (0.02%) alleles from individuals of European background (Lek et al., 2016). The E1957G 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 is predicted to be within the C-terminal cytoplasmic domain. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000537890 SCV000633877 uncertain significance Early infantile epileptic encephalopathy 2018-08-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 1957 of the SCN1A protein (p.Glu1957Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs121918802, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual with a SCN1A-related disease (PMID: 14504318). ClinVar contains an entry for this variant (Variation ID: 68671). 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: "Benign"; Align-GVGD: "Class C35"). This variant identified in the SCN1A gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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.
UniProtKB/Swiss-Prot RCV000059551 SCV000091083 not provided West syndrome no assertion provided not provided

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