ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3997G>A (p.Ala1333Thr)

dbSNP: rs796053132
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189145 SCV000242777 pathogenic not provided 2019-09-10 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Wolff et al., 2017); In silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect; This variant is associated with the following publications: (PMID: 28133863)
Labcorp Genetics (formerly Invitae), Labcorp RCV002514054 SCV003525056 pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-09-26 criteria provided, single submitter clinical testing 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 SCN2A protein function. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1333 of the SCN2A protein (p.Ala1333Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with early onset epileptic encephalopathy (PMID: 28133863). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 206994).

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