ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5555T>C (p.Met1852Thr)

dbSNP: rs121918783
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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 RCV000180879 SCV000221848 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000180879 SCV000996091 pathogenic Severe myoclonic epilepsy in infancy 2017-12-14 criteria provided, single submitter clinical testing This variant has been previously reported as disease causing in a patient with severe myoclonic epilepsy in infancy and in the patient's sibling with generalized epilepsy with febrile seizures (PMID: 12919402) and in an individual with Dravet syndrome (PMID: 26096185). The c.5555T>C (p.Met1852Thr) variant is absent from population databases, thus is presumed to be rare. Functional studies show that this change is a loss of function variant, specifically affecting cellular trafficking (PMID: 17928445). In silico algorithms predict this change to be deleterious. Based on the overall evidence the c.5555T>C (p.Met1852Thr) variant is classified as pathogenic.
Invitae RCV001854247 SCV002223528 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-02-21 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1852 of the SCN1A protein (p.Met1852Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 12919402, 26096185, 31019026). In at least one individual the variant was observed to be de novo. This variant is also known as p.Met1841Thr. ClinVar contains an entry for this variant (Variation ID: 68664). 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. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059544 SCV000091076 not provided Generalized epilepsy with febrile seizures plus, type 1 no assertion provided not provided

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