ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4789G>T (p.Asp1597Tyr) (rs121917915)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000059428 SCV000221832 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000584823 SCV000692549 pathogenic Seizures; Delayed speech and language development 2016-03-15 criteria provided, single submitter clinical testing
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000059428 SCV000693802 likely pathogenic Severe myoclonic epilepsy in infancy 2018-01-01 criteria provided, single submitter clinical testing
Invitae RCV000636349 SCV000757788 pathogenic Early infantile epileptic encephalopathy 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 1608 of the SCN1A protein (p.Asp1608Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with severe myoclonic epilepsy (PMID: 17561957) and an individual affected with early-onset epilepsy (Invitae). ClinVar contains an entry for this variant (Variation ID: 68554). This variant identified in the SCN1A gene is located in the transmembrane spanning D4-S3 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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. A different missense substitution at this codon (p.Asp1608Gly) has been reported to be de novo in an individual affected with severe myoclonic epilepsy (PMID: 23195492). This suggests that the aspartic acid residue is critical for SCN1A protein function. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059428 SCV000090952 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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