Submissions for variant NM_001165963.4(SCN1A):c.1625G>A (p.Arg542Gln)

gnomAD frequency: 0.00154  dbSNP: rs121918817

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118239	SCV000152599	likely benign	not specified	2018-10-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000118239	SCV000203514	likely benign	not specified	2017-06-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000118239	SCV000242442	benign	not specified	2017-02-02	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	RCV000475058	SCV000559699	benign	Early infantile epileptic encephalopathy with suppression bursts	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316218	SCV000849474	benign	Inborn genetic diseases	2019-04-03	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000789040	SCV000928381	uncertain significance	Severe myoclonic epilepsy in infancy	2019-10-04	criteria provided, single submitter	clinical testing	PP3, BS2
Mendelics	RCV000118239	SCV002519999	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000118239	SCV002766146	likely benign	not specified	2022-11-09	criteria provided, single submitter	clinical testing	Variant summary: SCN1A c.1625G>A (p.Arg542Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 251248 control chromosomes. The observed variant frequency is approximately 95 fold of the estimated maximal expected allele frequency for a pathogenic variant in SCN1A causing SCN1A-Related Seizure Disorder phenotype (1.8e-05), strongly suggesting that the variant is benign. Although reported in the literature, to our knowledge, no occurrence of c.1625G>A in individuals affected with SCN1A-Related Seizure Disorder and no conclusive experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments but a predominant consensus as benign/likely benign (n=7). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV001705717	SCV003916157	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	SCN1A: BS1
PreventionGenetics, part of Exact Sciences	RCV003915025	SCV004736287	likely benign	SCN1A-related condition	2020-04-24	criteria provided, single submitter	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).
UniProtKB/Swiss-Prot	RCV000059464	SCV000090989	unknown significance	Autism		no assertion criteria provided	not provided	Converted during submission to Uncertain significance.
Bioinformatics Core, Luxembourg Center for Systems Biomedicine	RCV000655983	SCV000588259	pathogenic	Childhood epilepsy with centrotemporal spikes	2017-01-01	flagged submission	case-control	CAADphred>15
GenomeConnect, ClinGen	RCV000578859	SCV000681394	not provided	Severe myoclonic epilepsy in infancy; Epilepsy		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252611	SCV001428370	likely benign	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001705717	SCV001928110	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118239	SCV001968061	benign	not specified		no assertion criteria provided	clinical testing