Submissions for variant NM_001040142.2(SCN2A):c.1269G>A (p.Val423=)

gnomAD frequency: 0.00662  dbSNP: rs139815570

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000118245	SCV000152612	uncertain significance	not provided	2013-04-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000212987	SCV000171527	benign	not specified	2013-01-15	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.
Illumina Laboratory Services, Illumina	RCV000267564	SCV000417401	benign	Seizures, benign familial infantile, 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079874	SCV000562153	benign	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312490	SCV000847034	benign	Inborn genetic diseases	2016-06-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Athena Diagnostics	RCV000212987	SCV001475475	benign	not specified	2020-06-26	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224154	SCV003920432	likely benign	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11; Episodic ataxia, type 9	2022-08-18	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 2% (852/41418) including 16 homozygotes (https://gnomad.broadinstitute.org/variant/2-165313994-G-A?dataset=gnomad_r3). This variant is present in ClinVar with several labs classifying this variant as Benign (Variation ID:130211). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.