Submissions for variant NM_001130438.3(SPTAN1):c.3599A>G (p.His1200Arg)

gnomAD frequency: 0.00001  dbSNP: rs745798632

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000441970	SCV000526739	likely benign	not specified	2016-04-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001345703	SCV001539841	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2023-08-17	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPTAN1 protein function. ClinVar contains an entry for this variant (Variation ID: 385475). This variant has not been reported in the literature in individuals affected with SPTAN1-related conditions. This variant is present in population databases (rs745798632, gnomAD 0.006%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1200 of the SPTAN1 protein (p.His1200Arg).
Genome-Nilou Lab	RCV001808816	SCV002056560	uncertain significance	Developmental and epileptic encephalopathy, 5	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002525397	SCV003645637	likely benign	Inborn genetic diseases	2022-08-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.