ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5870A>G (p.Glu1957Gly) (rs121918802)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000416094 SCV000242655 benign not provided 2020-02-14 criteria provided, single submitter clinical testing Reported previously an individual with infantile spasms and mild intellectual disability; however, family studies were not performed (Wallace et al., 2003); This substitution is within the C-terminal cytoplasmic domain of the protein (Escayg et al., 2010); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23527921, 14504318)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000416094 SCV000493672 uncertain significance not provided 2016-07-31 criteria provided, single submitter clinical testing
Invitae RCV000537890 SCV000633877 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 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.
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
UniProtKB/Swiss-Prot RCV000059551 SCV000091083 not provided West syndrome no assertion provided not provided

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