Submissions for variant NM_000335.5(SCN5A):c.4639G>A (p.Glu1547Lys)

gnomAD frequency: 0.00001  dbSNP: rs199473271

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations	RCV000058694	SCV005081697	likely pathogenic	Brugada syndrome	2024-07-17	criteria provided, single submitter	clinical testing	Heterozygous variant NM_198056.3:c.4642G>A in the SCN5A gene was found on NGS data in asymptomatic male proband (6 y.o., Caucasian) with spontaneous Brugada pattern on ECG and unremarkable clinical history (PMID: 36091819). This variant is in The Genome Aggregation Database (gnomAD) v2.1.1 and v4.1.0 with total MAF 0.00003185 and 6.196e-7 respectively (Date of access 17-07-2024). Clinvar contains an entry for this variant (Variation ID: 67913). Most in silico predictors show pathogenic result of the protein change (varsome.com). In accordance with ACMG(2015) criteria and Enhanced rare variant interpretation in inherited arrhythmias (PMID: 32893267) this variant is classified as Likely Pathogenic with following criteria selected: PM1_Strong, PM2, PP3, PP5.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058694	SCV000090214	not provided	Brugada syndrome		no assertion provided	literature only	This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.