Submissions for variant NM_001040142.2(SCN2A):c.742C>A (p.Leu248Ile)

dbSNP: rs1697362478

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001229678	SCV001402132	uncertain significance	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2019-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with isoleucine at codon 248 of the SCN2A protein (p.Leu248Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN2A-related conditions. 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"). 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.
CeGaT Center for Human Genetics Tuebingen	RCV001815520	SCV002063906	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing