| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R1636Q | Lennox-Gastaut syndrome | High | 6 | 17347258 |
| SCN4A | R1448S | Paramyotonia congenita | High | 6 | 10381583 |
| SCN4A | R1448C | Paramyotonia congenita | High | 6 | 1316765, 8110459, 8005599, 7809121 |
| SCN4A | R1448H | Paramyotonia congenita | High | 6 | 1316765, 22507243, 24843232, 8110459, 8005599, 12562902, 7809121 |
| SCN4A | R1448P | Myotonia | High | 6 | 7676326, 20038812 |
| SCN4A | R1448L | Paramyotonia congenita | High | 6 | 18166706 |
| CACNA1F | R1296S | Night blindness, congenital stationary, incomplete | High | 6 | 15761389, 25525159 |
| CACNA1A | R1662H | Episodic ataxia 2 | High | 6 | 10987655, 26814174 |
| SCN8A | R1617Q | Intellectual disability, nonsyndromic | High | 6 | 23020937, 24888894, 25785782, 25046240, 26900580 |
| SCN2A | R1626Q | Seizures, benign infantile | High | 6 | 25473036, 25937001 |
| CACNA1F | R1296C | Night blindness, congenital stationary, incomplete | High | 6 | 25307992 |
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 | ---------------------KYFFSPTLF>R<VIRLARIGRILRLIRGAKGIRTLLFALMMS | 1653 |
| SCN1A | ---------------------KYFVSPTLF>R<VIRLARIGRILRLIKGAKGIRTLLFALMMS | 1666 |
| SCN2A | ---------------------KYFVSPTLF>R<VIRLARIGRILRLIKGAKGIRTLLFALMMS | 1656 |
| SCN3A | ---------------------KYFVSPTLF>R<VIRLARIGRILRLIKGAKGIRTLLFALMMS | 1651 |
| SCN4A | ---------------------KYFVSPTLF>R<VIRLARIGRVLRLIRGAKGIRTLLFALMMS | 1478 |
| SCN7A | ---------------------SYLVPPSLV>Q<LILLSRIIHMLRLGKGPKVFHNLMLPLMLS | 1376 |
| SCN8A | ---------------------KYFVSPTLF>R<VIRLARIGRILRLIKGAKGIRTLLFALMMS | 1647 |
| SCN9A | ---------------------TYFVSPTLF>R<VIRLARIGRILRLVKGAKGIRTLLFALMMS | 1629 |
| SCN10A | --------------------LQSYFSPTLF>R<VIRLARIGRILRLIRAAKGIRTLLFALMMS | 1603 |
| SCN11A | --------------------EHIPFPPTLF>R<IVRLARIGRILRLVRAARGIRTLLFALMMS | 1493 |
| CACNA1A | -----------------------FINLSFL>R<LFRA---ARLIKLLRQGYTIRILLWTFVQS | 1688 |
| CACNA1B | ---------------------NNFINLSFL>R<LFRA---ARLIKLLRQGYTIRILLWTFVQS | 1596 |
| CACNA1C | E----HTQ----CSPSMNAEENSRISITFF>R<LFRV---MRLVKLLSRGEGIRTLLWTFIKS | 1356 |
| CACNA1D | E----SENVPVPTATPGNSEESNRISITFF>R<LFRV---MRLVKLLSRGEGIRTLLWTFIKS | 1366 |
| CACNA1E | --------------------NTSGFNMSFL>K<LFRA---ARLIKLLRQGYTIRILLWTFVQS | 1603 |
| CACNA1F | G----HLG----E----SSEDSSRISITFF>R<LFRV---MRLVKLLSKGEGIRTLLWTFIKS | 1323 |
| CACNA1G | --------------------ASLPINPTII>R<IMRVLRIARVLKLLKMAVGMRALLDTVMQA | 1739 |
| CACNA1H | --------------------AALPINPTII>R<IMRVLRIARVLKLLKMATGMRALLDTVVQA | 1745 |
| CACNA1I | --------------------AALPINPTII>R<IMRVLRIARVLKLLKMATGMRALLDTVVQA | 1615 |
| CACNA1S | LASSGGLYCLGGGCGNVDPDESARISSAFF>R<LFRV---MRLIKLLSRAEGVRTLLWTFIKS | 1263 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R1623L | c.4868G>T | Inherited Arrhythmia | LQTS | rs137854600 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | ||
| Inherited Arrhythmia | LQTS | Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005 2(5):507-17. 15840476 | |||
| Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | |||
| p.R1623Q | c.4868G>A | Inherited Arrhythmia | LQTS,BrS | rs137854600 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Phenotypic characterization of a novel long-QT syndrome mutation (R1623Q) in the cardiac sodium channel. Circulation. 1998 97(7):640-4. 9495298 | ||
| Inherited Arrhythmia | LQTS | A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome. FEBS Lett. 1998 423(1):5-9. 9506831 | |||
| Other Cardiac Phenotype | A de novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT sydrome. Mutations in brief no. 140. Online. Hum Mutat. 1998 11(6):481. 10200053 | ||||
| Inherited Arrhythmia | LQTS | Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 102(10):1178-85. 10973849 | |||
| Inherited Arrhythmia | LQTS | Congenital long QT syndrome and 2:1 atrioventricular block with a mutation of the SCN5A gene. Pediatr Cardiol. 2003 24(1):70-2. 12574983 | |||
| Inherited Arrhythmia | LQTS | Compound mutations: a common cause of severe long-QT syndrome. Circulation. 2004 109(15):1834-41. 15051636 | |||
| Inherited Arrhythmia | LQTS | Recurrent third-trimester fetal loss and maternal mosaicism for long-QT syndrome. Circulation. 2004 109(24):3029-34. 15184283 | |||
| Inherited Arrhythmia | LQTS | Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006 70(3):214-27. 16922724 | |||
| Inherited Arrhythmia | LQTS | Differential modulation of late sodium current by protein kinase A in R1623Q mutant of LQT3. Life Sci. 2009 84(11-12):380-7. 19167409 | |||
| Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | |||
| Inherited Arrhythmia | LQTS | Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300 | |||
| Inherited Arrhythmia | LQTS | Impaired stretch modulation in potentially lethal cardiac sodium channel mutants. Channels (Austin). 2010 4(1):12-21. 20090423 | |||
| 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 | LQTS | A revised view of cardiac sodium channel "blockade" in the long-QT syndrome. J Clin Invest. 2000 105(8):1133-40. 10772658 | |||
| 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 | |||
| Inherited Arrhythmia | Efficacy of an implantable cardioverter-defibrillator in a neonate with LQT3 associated arrhythmias. Europace. 2005 7(1):77-84. 15670972 | ||||