ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4502T>C (p.Met1501Thr)

dbSNP: rs1553462227
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000640627 SCV000762221 pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-01-23 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 1501 of the SCN2A protein (p.Met1501Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN2A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 533495). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003225104 SCV003921738 likely pathogenic not provided 2022-10-31 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 has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be in the cytoplasmic loop between the third and fourth homologous domains
GenomeConnect - Simons Searchlight RCV001265263 SCV001443379 likely pathogenic Complex neurodevelopmental disorder 2019-01-29 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-01-29 and interpreted as Likely Pathogenic. Variant was initially reported on 2017-08-29 by GTR ID of laboratory name 500031. The reporting laboratory might also submit to ClinVar.
Department of Neurology, Children’s Hospital of Chongqing Medical University RCV003155954 SCV002577335 likely pathogenic unclassified developmental and epileptic encephalopathy no assertion criteria provided research

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