ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2539T>C (p.Ser847Pro)

dbSNP: rs1699366480
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001064072 SCV001228948 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2021-09-02 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003985480 SCV004118690 likely pathogenic SCN2A-related disorder 2022-09-29 criteria provided, single submitter clinical testing The SCN2A c.2539T>C variant is predicted to result in the amino acid substitution p.Ser847Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been confirmed de novo in an individual with infantile-onset seizures (Internal Data, PreventionGenetics, LCC). This variant is interpreted as likely pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV005208155 SCV005849343 uncertain significance Seizures, benign familial infantile, 3 2023-06-22 criteria provided, single submitter clinical testing The missense variant c.2539T>C (p.Ser847Pro) in the SCN2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is absent in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Ser at position 847 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen - Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Ser847Pro in SCN2A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance

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