Submissions for variant NM_006922.4(SCN3A):c.5584G>T (p.Gly1862Cys)

gnomAD frequency: 0.01346  dbSNP: rs41265137

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Epilepsy Sodium Channel Variant Curation Expert Panel, Clingen	RCV004577519	SCV005061726	benign	Early infantile epileptic encephalopathy with suppression bursts	2024-05-09	reviewed by expert panel	curation	The c.5584G>T variant in SCN3A is a missense variant predicted to case the substitution of glycine by cysteine at amino acid 1862 (p.Gly1862Cys). The highest population minor allele frequency in gnomAD v.2 is 8.2% (2915/35374 alleles) in the Latino population, which is higher than the ClinGen Epilepsy Sodium Channel threshold (0.3%) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.808 (PP3_Moderate). Although there are both pathogenic and benign types of evidence for this variant, the high frequency of this variant in gnomAD strongly supports a benign classification, and the only evidence in support of pathogenicity is based on a computational predictor that should not override the high population frequency, which precludes this variant from being pathogenic for a rare disease. In summary, this variant meets the criteria to be classified as Benign for autosomal dominant developmental and epileptic encephalopathy based on ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: BA1 and PP3_Moderate. (VCEP specifications version 1; 6/27/2023).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000234605	SCV000289609	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000234605	SCV001858229	benign	not provided	2021-05-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000234605	SCV005239563	benign	not provided		criteria provided, single submitter	not provided