ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4918A>T (p.Ile1640Phe)

dbSNP: rs1702006673
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001036227 SCV001199579 likely pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2019-05-08 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ile1640 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been observed in individuals with SCN2A-related conditions (PMID: 28379373), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individuals with clinical features of early infantile epileptic encephalopathy (PMID: 30619928, Invitae). In at least one individual the variant was found to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 1640 of the SCN2A protein (p.Ile1640Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine.
Centogene AG - the Rare Disease Company RCV001809957 SCV002059718 likely pathogenic Developmental and epileptic encephalopathy, 11 2019-05-08 criteria provided, single submitter clinical testing

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