|(G;G)||0||common in clinvar|
|(G;T)||2||Now: Benign? Formerly: increased susceptibility to long QT syndrome|
|(T;T)||2||Now: Benign? Formerly: increased susceptibility to long QT syndrome|
rs7626962, also known as Ser1103Tyr or S1103Y, is a SNP in the cardiac sodium channel SCN5A gene.
Although relatively common (for a rare allele; 10 - 20% of individuals) in those of African ancestry, in all populations the rs7626962(T) allele has been reported to increase the risk for cardiac issues such as long QT syndrome but also arrhythmias and even sudden infant death syndrome.
The odds ratio for displaying signs of arrhythmia for anyone carrying a rs7626962(T) allele is reported as 8.7 (CI 3.2 - 23.9) [PMID 12193783]; as for sudden infant death syndrome, at least in African-ancestry populations, the odds ratio for the same allele is reported as 4.9, leading to an odds ratio of 24 for rs7626962(T;T) homozygotes.[PMID 16453024]
This variant meets the criteria published in 2013 by the ACMG regarding incidental findings in exome or genome sequencing, as a variant that they do recommend informing a patient about.[PMID 23788249]
Note, however, that as of 2015/2016, this variant has been re-classified as either benign or likely benign in ClinVar (by two labs), so the clinical significance is quite unclear.
[PMID 19214780] In silico investigations on functional and haplotype tag SNPs associated with congenital long QT syndromes (LQTSs).
[PMID 19530973] Genetic variation in the rhythmonome: ethnic variation and haplotype structure in candidate genes for arrhythmias.
[PMID 21347284] Genome-wide association studies of the PR interval in African Americans.
[PMID 12193783] Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia.
[PMID 15161528] Single nucleotide polymorphisms of the SCN5A gene in Han Chinese and their relation with Brugada syndrome.
[PMID 19841300] Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants.
|qualified_impact||Insufficiently evaluated pathogenic|
|summary||This is a common variant in individuals of African descent (African American allele frequency 6.8%). It is associated with an increased risk of cardiac arrhythmia (odds ratio of 8.7 for both homozygous and heterozygous carriers) and of sudden infant death syndrome (24-fold increase for homozygous).|