ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5126C>T (p.Thr1709Ile)

dbSNP: rs121918629
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001296128 SCV001485084 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-11-29 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with generalized epilepsy with febrile seizures plus (GEFS+) or Dravet syndrome (PMID: 12566275, 15277629). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1709 of the SCN1A protein (p.Thr1709Ile). ClinVar contains an entry for this variant (Variation ID: 12894). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Thr1709 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 28202706), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects SCN1A function (PMID: 16210358). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function.
OMIM RCV000013754 SCV000034001 pathogenic Severe myoclonic epilepsy in infancy 2003-03-01 no assertion criteria provided literature only
OMIM RCV000013755 SCV000034002 pathogenic Generalized epilepsy with febrile seizures plus, type 2 2003-03-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000013754 SCV000091062 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided
Channelopathy-Associated Epilepsy Research Center RCV000013754 SCV004809292 not provided Severe myoclonic epilepsy in infancy no assertion provided literature only

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