ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2665G>A (p.Ala889Thr)

dbSNP: rs1266877537
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001696832 SCV000621064 likely pathogenic not provided 2020-06-22 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Substitution predicted to be within the transmembrane segment S5 of the second homologous domain; This variant is associated with the following publications: (PMID: 31487502, 30336400)
Labcorp Genetics (formerly Invitae), Labcorp RCV000559503 SCV000633833 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-11-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 452271). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 31487502; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 889 of the SCN1A protein (p.Ala889Thr).
Institute of Human Genetics, University of Leipzig Medical Center RCV001253601 SCV001429410 likely pathogenic Severe myoclonic epilepsy in infancy 2019-02-04 criteria provided, single submitter clinical testing

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