Submissions for variant NM_000335.5(SCN5A):c.3973G>T (p.Ala1325Ser)

dbSNP: rs199473222

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183188	SCV000235606	pathogenic	not provided	2014-10-02	criteria provided, single submitter	clinical testing	p.Ala1326Ser (GCC>TCC): c.3976 G>T in exon 23 of the SCN5A gene (NM_198056.2) The A1326S mutation in the SCN5A gene has been reported in association with LQTS and was absent from at least 2,600 reference alleles (Kapplinger et al., 2009). A1326S results in a non-conservative amino acid substitution of Alanine at a position that is conserved across species. Mutations in nearby residues (V1323G, N1325S, A1330P, A1330T) have been reported in association with familial forms of arrhythmia, further supporting the functional importance of this region of the protein. Furthermore, the A1326S mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, A1326S in the SCN5A gene is interpreted as a disease-causing mutation. The variant is found in ARRHYTHMIA panel(s).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058619	SCV000090139	not provided	Congenital long QT syndrome		no assertion provided	literature only	This variant has been reported as associated with Long QT syndrome in the following publications (PMID:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.