Submissions for variant NM_001165963.4(SCN1A):c.4129A>G (p.Ile1377Val)

gnomAD frequency: 0.00016  dbSNP: rs762317674

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725944	SCV000340713	uncertain significance	not provided	2016-04-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000725944	SCV000589462	likely benign	not provided	2020-06-03	criteria provided, single submitter	clinical testing	The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the third homologous domain
Ambry Genetics	RCV002317815	SCV000849539	likely benign	Inborn genetic diseases	2017-05-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000794768	SCV000934196	likely benign	Early infantile epileptic encephalopathy with suppression bursts	2025-01-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004734934	SCV005346706	likely benign	SCN1A-related disorder	2024-07-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).