ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4940C>T (p.Thr1647Met) (rs121917922)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000059523 SCV000221965 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Invitae RCV000529623 SCV000633868 uncertain significance Early infantile epileptic encephalopathy 2017-07-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1658 of the SCN1A protein (p.Thr1658Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in 2 individuals affected with Dravet syndrome (PMID: 18930999, 20522430). ClinVar contains an entry for this variant (Variation ID: 68643). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant identified in the SCN1A gene is located in the cytoplasmic D4-S4/S5 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.
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000059523 SCV000693792 likely pathogenic Severe myoclonic epilepsy in infancy 2018-01-01 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059523 SCV000091054 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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