| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN2A | T1623N | Ohtahara syndrome | High | 7 | 23935176 |
To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in SCN5A.
| SCN5A | IQ----------------------KYFFSP>T<LFRVIRLARIGRILRLIRGAKGIRTLLFAL | 1650 |
| SCN1A | IE----------------------KYFVSP>T<LFRVIRLARIGRILRLIKGAKGIRTLLFAL | 1663 |
| SCN2A | IE----------------------KYFVSP>T<LFRVIRLARIGRILRLIKGAKGIRTLLFAL | 1653 |
| SCN3A | IE----------------------KYFVSP>T<LFRVIRLARIGRILRLIKGAKGIRTLLFAL | 1648 |
| SCN4A | IQ----------------------KYFVSP>T<LFRVIRLARIGRVLRLIRGAKGIRTLLFAL | 1475 |
| SCN7A | VG----------------------SYLVPP>S<LVQLILLSRIIHMLRLGKGPKVFHNLMLPL | 1373 |
| SCN8A | IE----------------------KYFVSP>T<LFRVIRLARIGRILRLIKGAKGIRTLLFAL | 1644 |
| SCN9A | IE----------------------TYFVSP>T<LFRVIRLARIGRILRLVKGAKGIRTLLFAL | 1626 |
| SCN10A | LKS--------------------LQSYFSP>T<LFRVIRLARIGRILRLIRAAKGIRTLLFAL | 1600 |
| SCN11A | ENQ--------------------EHIPFPP>T<LFRIVRLARIGRILRLVRAARGIRTLLFAL | 1490 |
| CACNA1A | GNN-----------------------FINL>S<FLRLFRA---ARLIKLLRQGYTIRILLWTF | 1685 |
| CACNA1B | AET---------------------NNFINL>S<FLRLFRA---ARLIKLLRQGYTIRILLWTF | 1593 |
| CACNA1C | NPAE----HTQ----CSPSMNAEENSRISI>T<FFRLFRV---MRLVKLLSRGEGIRTLLWTF | 1353 |
| CACNA1D | DPTE----SENVPVPTATPGNSEESNRISI>T<FFRLFRV---MRLVKLLSRGEGIRTLLWTF | 1363 |
| CACNA1E | KLV--------------------NTSGFNM>S<FLKLFRA---ARLIKLLRQGYTIRILLWTF | 1600 |
| CACNA1F | NNGG----HLG----E----SSEDSSRISI>T<FFRLFRV---MRLVKLLSKGEGIRTLLWTF | 1320 |
| CACNA1G | EVN--------------------ASLPINP>T<IIRIMRVLRIARVLKLLKMAVGMRALLDTV | 1736 |
| CACNA1H | EMS--------------------AALPINP>T<IIRIMRVLRIARVLKLLKMATGMRALLDTV | 1742 |
| CACNA1I | EIN--------------------AALPINP>T<IIRIMRVLRIARVLKLLKMATGMRALLDTV | 1612 |
| CACNA1S | DTFLASSGGLYCLGGGCGNVDPDESARISS>A<FFRLFRV---MRLIKLLSRAEGVRTLLWTF | 1260 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.T1620K | c.4859C>A | Inherited Arrhythmia | LQTS | rs199473282 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Combination of cardiac conduction disease and long QT syndrome caused by mutation T1620K in the cardiac sodium channel. Cardiovasc Res. 2008 77(4):740-8. 18065446 | ||
| Inherited Arrhythmia | LQTS | Alternative splicing of the cardiac sodium channel creates multiple variants of mutant T1620K channels. PLoS One. 2011 6(4):e19188. 21552533 | |||
| p.T1620M | c.4859C>T | Cardiomyopathy | BrS,DCM | rs199473282 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Other Cardiac Phenotype | Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 1998 392(6673):293-6. 9521325 | |||
| Inherited Arrhythmia | BrS | An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 7(1):33-46. 20129283 | |||
| Other Cardiac Phenotype | Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by beta(1)-subunit. Circulation. 2000 101(1):54-60. 10618304 | ||||
| Other Cardiac Phenotype | Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation. 2004 110(19):3023-7. 15520322 | ||||
| Other Cardiac Phenotype | Functional suppression of sodium channels by beta(1)-subunits as a molecular mechanism of idiopathic ventricular fibrillation. J Mol Cell Cardiol. 2000 32(10):1873-84. 11013131 | ||||
| Other Cardiac Phenotype | Expression and intracellular localization of an SCN5A double mutant R1232W/T1620M implicated in Brugada syndrome. Circ Res. 2002 90(1):E11-6. 11786529 | ||||
| Other Cardiac Phenotype | A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease. Cardiovasc Res. 2002 53(2):348-54. 11827685 | ||||
| Cardiomyopathy | DCM | Targeted sequence capture and GS-FLX Titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics. J Med Genet. 2013 50(9):614-26. doi: 10.1136/jmedgenet-2012-101231. 23785128 | |||