|(C;C)||0||common in clinvar|
|(C;T)||3||possible susceptibility to long QT syndrome|
|(T;T)||4||possible susceptibility to long QT syndrome|
It is unclear how penetrant (causative) the rare allele of this SNP is for cardiac issues such as long QT syndrome. It was thought to be causative, based on observations in Caucasians, but then a report came out stating that 14% of Han Chinese carry this variant, most without any apparent problem. See OMIM and the GetEvidence summary below on right for more discussion.
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]
|Disease||Brugada syndrome 1 Long qt syndrome 3 not provided not specified Primary familial hypertrophic cardiomyopathy Brugada syndrome Cardiovascular phenotype|
|CLNDBN||Brugada syndrome 1 Long qt syndrome 3, acquired, susceptibility to not provided not specified Primary familial hypertrophic cardiomyopathy Brugada syndrome Cardiovascular phenotype|
|CLNSRC||OMIM Allelic Variant|
|CLNACC||RCV000009990.5, RCV000009991.4, RCV000058578.6, RCV000154828.2, RCV000157488.1, RCV000171819.5, RCV000252422.1,|
[PMID 16155] Cryptorchidism and abdominal pain.
[PMID 11823453] Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome.
[PMID 12639704] Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects.
[PMID 15121794] The common SCN5A mutation R1193Q causes LQTS-type electrophysiological alterations of the cardiac sodium channel.
[PMID 15689442] R1193Q of SCN5A, a Brugada and long QT mutation, is a common polymorphism in Han Chinese.
[PMID 15851227] Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing.
|qualified_impact||Moderate clinical importance, Uncertain pathogenic|
|summary||Proposed as a dominant cause of rare heart arrhythmia diseases (Brugada Syndrome and Long QT Syndrome). This has since been contradicted by the high frequency of this variant in the Han Chinese population. 14% of Chinese are carriers, contradicting this variant as a high penetrance cause of rare disease. It is possible the variant is associated with low increased risk of Long QT syndrome, but this is a speculative and untested hypothesis.|