ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5639G>A (p.Gly1880Glu) (rs201905405)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000488340 SCV000242644 uncertain significance not provided 2018-01-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1A gene. The G1880E variant has been previously identified in several individuals with classic Dravet syndrome, although parental testing was not performed and additional details were not provided (Zuberi et al., 2011, Catarino et al., 2011, Parihar et al., 2013). The G1880E variant is observed in 20/125,802 (0.02%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The G1880E variant is a non-conservative amino acid substitution, which is likely to impact secondary proteinstructure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Thissubstitution is predicted to be within the C-terminal cytoplasmic domain. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000488340 SCV000341238 uncertain significance not provided 2016-04-21 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488340 SCV000575245 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Invitae RCV000692247 SCV000820060 uncertain significance Early infantile epileptic encephalopathy 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 1880 of the SCN1A protein (p.Gly1880Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs201905405, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individuals affected with Dravet syndrome (PMID: 21248271). ClinVar contains an entry for this variant (Variation ID: 206875). 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 C65"). 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.
Illumina Clinical Services Laboratory,Illumina RCV001136462 SCV001296300 uncertain significance Familial hemiplegic migraine type 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001136463 SCV001296301 uncertain significance Generalized epilepsy with febrile seizures plus, type 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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