| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN4A | P1158S | Hypokalaemic periodic paralysis | High | 9 | 10851391 |
| SCN9A | P1308L | Erythermalgia, primary | High | 9 | 20429905 |
| SCN1A | P1345S | Epileptic encephalopathy, early onset | High | 9 | 23708187 |
| SCN1A | P1345L | Epilepsy of infancy with migrating focal seizures | High | 9 | 26993267 |
| SCN4A | P1158L | Myotonia | High | 9 | 27164696 |
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 | LRTLRALRPLRALSRFEGMRVVVNALVGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFGR | 1362 |
| SCN1A | LRTLRALRPLRALSRFEGMRVVVNALLGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFYH | 1375 |
| SCN2A | LRTLRALRPLRALSRFEGMRVVVNALLGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFYH | 1365 |
| SCN3A | LRTLRALRPLRALSRFEGMRVVVNALVGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFYH | 1363 |
| SCN4A | LRTLRALRPLRALSRFEGMRVVVNALLGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFYY | 1188 |
| SCN7A | LISMKFLRPLRVLSQFERMKVVVRALIKTT>L<PTLNVFLVCLMIWLIFSIMGVDLFAGRFYE | 1086 |
| SCN8A | LRTLRALRPLRALSRFEGMRVVVNALVGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKYHY | 1355 |
| SCN9A | LRTLRALRPLRALSRFEGMRVVVNALIGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFYE | 1338 |
| SCN10A | LRTLRALRPLRALSRFEGMRVVVDALVGAI>P<SIMNVLLVCLIFWLIFSIMGVNLFAGKFWR | 1309 |
| SCN11A | FRTLRALRPLRALSQFEGMKVVVNALIGAI>P<AILNVLLVCLIFWLVFCILGVYFFSGKFGK | 1206 |
| CACNA1A | LRVLRVLRPLKTIKRLPKLKAVFDCVVNSL>K<NVFNILIVYMLFMFIFAVVAVQLFKGKFFH | 1405 |
| CACNA1B | LRVLRVLRPLKTIKRLPKLKAVFDCVVNSL>K<NVLNILIVYMLFMFIFAVIAVQLFKGKFFY | 1311 |
| CACNA1C | LRVLRVLRPLRAINRAKGLKHVVQCVFVAI>R<TIGNIVIVTTLLQFMFACIGVQLFKGKLYT | 1057 |
| CACNA1D | LRVLRVLRPLRAINRAKGLKHVVQCVFVAI>R<TIGNIMIVTTLLQFMFACIGVQLFKGKFYR | 1063 |
| CACNA1E | LRVLRVLRPLKTIKRLPKLKAVFDCVVTSL>K<NVFNILIVYKLFMFIFAVIAVQLFKGKFFY | 1317 |
| CACNA1F | LRVLRVLRPLRAINRAKGLKHVVQCVFVAI>R<TIGNIMIVTTLLQFMFACIGVQLFKGKFYT | 1028 |
| CACNA1G | LRLLRTLRPLRVISRAQGLKLVVETLMSSL>K<PIGNIVVICCAFFIIFGILGVQLFKGKFFV | 1440 |
| CACNA1H | LRLLRTLRPLRVISRAPGLKLVVETLISSL>R<PIGNIVLICCAFFIIFGILGVQLFKGKFYY | 1458 |
| CACNA1I | LRLLRTLRPLRVISRAPGLKLVVETLISSL>K<PIGNIVLICCAFFIIFGILGVQLFKGKFYH | 1334 |
| CACNA1S | LRVLRVLRPLRAINRAKGLKHVVQCMFVAI>S<TIGNIVLVTTLLQFMFACIGVQLFKGKFFR | 956 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.P1332L | c.3995C>T | Inherited Arrhythmia | LQTS,BrS | rs199473225 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Long QT syndrome and life threatening arrhythmia in a newborn: molecular diagnosis and treatment response. Heart. 2004 90(1):13-6. 14676229 | ||
| Inherited Arrhythmia | LQTS | Images in cardiovascular medicine. Life-threatening neonatal arrhythmia: successful treatment and confirmation of clinically suspected extreme long QT-syndrome-3. Circulation. 2004 109(18):e205-6. 15136511 | |||
| Inherited Arrhythmia | LQTS | Gating properties of SCN5A mutations and the response to mexiletine in long-QT syndrome type 3 patients. Circulation. 2007 116(10):1137-44. 17698727 | |||
| Inherited Arrhythmia | LQTS | Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers. Scand J Clin Lab Invest. 2008 68(5):362-8. 18752142 | |||
| 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 | |||
| Inherited Arrhythmia | BrS | Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. J Med Genet. 2014 51(1):35-44. doi: 10.1136/jmedgenet-2013-101917. 24136861 | |||
| p.Pro1332Arg | c.3995C>G | Unknown | SIFT: Polyphen: | ||
| p.Pro1332Ser | c.3994C>T | Unknown | SIFT: Polyphen: | ||