ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4722C>A (p.Phe1574Leu)

dbSNP: rs1558884200
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768071 SCV000898956 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2018-11-28 criteria provided, single submitter clinical testing SCN2A NM_021007.2 exon 26 p.Phe1574Leu (c.4722C>A): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000768071 SCV001376576 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-02-17 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1574 of the SCN2A protein (p.Phe1574Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 626008). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224424 SCV003920427 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11; Episodic ataxia, type 9 2021-03-30 criteria provided, single submitter clinical testing SCN2A NM_021007.2 exon 26 p.Phe1574Leu (c.4722C>A): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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