Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
---|---|---|---|---|---|
SCN1A | R118S | Myoclonic epilepsy of infancy | High | 9 | 18413471 |
CACNA1F | R82Q | Congenital stationary night blindness | High | 9 | 25307992 |
CACNA1F | R82X | Night blindness, congenital stationary, incomplete | High | 9 | 11281458, 25525159 |
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 | TFI-VLNKGKTIFRFSATNALYVLSPFHPI>R<RAAVKILVHSLFNMLIMCTILTNCVFMAQH | 151 |
SCN1A | TFI-VLNKGKAIFRFSATSALYILTPFNPL>R<KIAIKILVHSLFSMLIMCTILTNCVFMTMS | 148 |
SCN2A | TFI-VLNKGKAISRFSATPALYILTPFNPI>R<KLAIKILVHSLFNMLIMCTILTNCVFMTMS | 149 |
SCN3A | TFI-VMNKGKAIFRFSATSALYILTPLNPV>R<KIAIKILVHSLFSMLIMCTILTNCVFMTLS | 148 |
SCN4A | TFI-VLNKGKAIFRFSATPALYLLSPFSVV>R<RGAIKVLIHALFSMFIMITILTNCVFMTMS | 151 |
SCN7A | TFI-VLNKNRTIFRFNAASILCTLSPFNCI>R<RTTIKVLVHPFFQLFILISVLIDCVFMSLT | 138 |
SCN8A | TFV-VLNRGKTLFRFSATPALYILSPFNLI>R<RIAIKILIHSVFSMIIMCTILTNCVFMTFS | 152 |
SCN9A | TFI-VLNKGKTIFRFNATPALYMLSPFSPL>R<RISIKILVHSLFSMLIMCTILTNCIFMTMN | 146 |
SCN10A | TFM-VLNKGRTISRFSATRALWLFSPFNLI>R<RTAIKVSVHSWFSLFITVTILVNCVCMTRT | 150 |
SCN11A | TFM-VLNRKRTIYRFSAKHALFIFGPFNSI>R<SLAIRVSVHSLFSMFIIGTVIINCVFMATG | 149 |
CACNA1A | MAL-YNPIPVRQNCLTVNRSLFLFSEDNVV>R<KYAKKITEWPPFEYMILATIIANCIVLALE | 118 |
CACNA1B | MAL-YNPIPVKQNCFTVNRSLFVFSEDNVV>R<KYAKRITEWPPFEYMILATIIANCIVLALE | 115 |
CACNA1C | QYG-KPKKQGSTTATRPPRALLCLTLKNPI>R<RACISIVEWKPFEIIILLTIFANCVALAIY | 144 |
CACNA1D | QYA-KSKKQGNSSNSRPARALFCLSLNNPI>R<RACISIVEWKPFDIFILLAIFANCVALAIY | 146 |
CACNA1E | MAL-YNPIPVRQNCFTVNRSLFIFGEDNIV>R<KYAKKLIDWPPFEYMILATIIANCIVLALE | 109 |
CACNA1F | QHS-KHKTVAVASAQRSPRALFCLTLANPL>R<RSCISIVEWKPFDILILLTIFANCVALGVY | 112 |
CACNA1G | G-SADSEAEGLPYPALAPVVFFYLSQDSRP>R<SWCLRTVCNPWFERISMLVILLNCVTLGMF | 101 |
CACNA1H | ELG-ADEEQRVPYPALAATVFFCLGQTTRP>R<SWCLRLVCNPWFEHVSMLVIMLNCVTLGMF | 120 |
CACNA1I | L-D-G-ADPHVPHPDLAPIAFFCLRQTTSP>R<NWCIKMVCNPWFECVSMLVILLNCVTLGMY | 99 |
CACNA1S | RKK-QPKKPVPEILPRPPRALFCLTLENPL>R<KACISIVEWKPFETIILLTIFANCVALAVY | 71 |
cons | > < |
Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
---|---|---|---|---|---|
p.R121Q | c.362G>A | Inherited Arrhythmia | BrS | rs199473058 | SIFT: deleterious Polyphen: probably damaging |
Reports | 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.R121W | c.361C>T | Inherited Arrhythmia | BrS | rs199473556 | SIFT: deleterious Polyphen: probably damaging |
Reports | Inherited Arrhythmia | BrS | The genetic basis of Brugada syndrome: a mutation update. Hum Mutat. 2009 30(9):1256-66. 19606473 | ||
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 | Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation. Cardiology. 2010 115(4):311-6. 20395683 | ||||
Inherited Arrhythmia | BrS | Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Nav1.5 α-subunits. Cardiovasc Res. 2012 96(1):53-63. 22739120 | |||
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 |