ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5468T>C (p.Met1823Thr)

dbSNP: rs1559101839
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693631 SCV000821506 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2024-02-23 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 1823 of the SCN1A protein (p.Met1823Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SCN1A-related conditions (PMID: 24679980, 31031587). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 572287). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN1A protein function. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001200252 SCV001371157 likely pathogenic not provided 2020-11-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001253286 SCV001428932 pathogenic Severe myoclonic epilepsy in infancy 2017-11-03 criteria provided, single submitter clinical testing
GeneDx RCV001200252 SCV004030703 pathogenic not provided 2023-03-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This substitution is predicted to be within the C-terminal cytoplasmic domain; This variant is associated with the following publications: (PMID: 24679980, 31031587, 36471706)

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