Submissions for variant NM_001330260.2(SCN8A):c.4966C>T (p.Leu1656Phe)

dbSNP: rs1938704933

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001218421	SCV001390303	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2019-06-13	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN8A-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. This sequence change replaces leucine with phenylalanine at codon 1656 of the SCN8A protein (p.Leu1656Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine.
Pediatrics Genetics, Post Graduate Institute of Medical Education and Research	RCV003329382	SCV004036032	uncertain significance	Developmental and epileptic encephalopathy, 13	2023-09-12	criteria provided, single submitter	clinical testing	This variant is not reported in 1000G, ExAC and insilico prediction is damaging by various tools.