Submissions for variant NM_001040142.2(SCN2A):c.1396_1401dup (p.Ala466_Ala467dup)

dbSNP: rs754615123

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001038103	SCV001201551	uncertain significance	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2024-08-11	criteria provided, single submitter	clinical testing	This variant, c.1396_1401dup, results in the insertion of 2 amino acid(s) of the SCN2A protein (p.Ala466_Ala467dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754615123, gnomAD 0.02%). 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: 836884). 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.
Revvity Omics, Revvity	RCV003141948	SCV003820778	uncertain significance	not provided	2022-10-26	criteria provided, single submitter	clinical testing
GeneDx	RCV003141948	SCV004170139	uncertain significance	not provided	2023-04-06	criteria provided, single submitter	clinical testing	In-frame insertion of 2 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the cytoplasmic loop between the first and second homologous domains
Neuberg Centre For Genomic Medicine, NCGM	RCV005208154	SCV005849382	uncertain significance	Developmental and epileptic encephalopathy, 11		criteria provided, single submitter	clinical testing	The observed inframe insertion variant c.1396_1401dup(p.Ala466_Ala467dup) in SCN2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0.002% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. This variant p.Ala466_Ala467dup causes duplication of amino acid Alanine at position 466 and Alanine at position 467. For these reasons, this variant has been classified as Uncertain Significance.