Submissions for variant NM_001040142.2(SCN2A):c.1724C>T (p.Ala575Val)

gnomAD frequency: 0.00001  dbSNP: rs986167267

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002037441	SCV002116010	uncertain significance	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2023-06-25	criteria provided, single submitter	clinical testing	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. Experimental studies have shown that this missense change does not substantially affect SCN2A function (PMID: 19786696). 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 not expected to disrupt SCN2A protein function. ClinVar contains an entry for this variant (Variation ID: 1345642). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 19786696). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 575 of the SCN2A protein (p.Ala575Val).
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003992567	SCV004809366	uncertain significance	Episodic ataxia, type 9	2024-04-04	criteria provided, single submitter	clinical testing