| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN4A | R675Q | Normokalaemic periodic paralysis | High | 9 | 15596759, 19065518, 22926674, 19052238, 19225109, 18046642, 25839108, 24682880 |
| SCN4A | R675G | Normokalaemic periodic paralysis | High | 9 | 15596759, 22926674, 19052238 |
| SCN4A | R675W | Normokalaemic periodic paralysis | High | 9 | 15596759, 19052238 |
| SCN1A | R865G | Dravet syndrome | High | 9 | 21864321, 24277604 |
| SCN1A | R865X | Myoclonic epilepsy of infancy | High | 9 | 12083760, 21868258, 23195492, 25525159 |
| SCN8A | R850Q | Intellectual disability and epilepsy | High | 9 | 25785782 |
| SCN2A | R856L | Epilepsy of infancy with migrating focal seizures | High | 9 | 26291284 |
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 | VILSLMELGLSRMS-----NLSVLRSFRLL>R<VFKLAKSWPTLNTLIKIIGNSVGALGNLTL | 844 |
| SCN1A | VTLSLVELGLANVE-----GLSVLRSFRLL>R<VFKLAKSWPTLNMLIKIIGNSVGALGNLTL | 895 |
| SCN2A | VSLSLMELGLANVE-----GLSVLRSFRLL>R<VFKLAKSWPTLNMLIKIIGNSVGALGNLTL | 886 |
| SCN3A | VSLSLMELGLSNVE-----GLSVLRSFRLL>R<VFKLAKSWPTLNMLIKIIGNSVGALGNLTL | 887 |
| SCN4A | VTLSLVELGLANVQ-----GLSVLRSFRLL>R<VFKLAKSWPTLNMLIKIIGNSVGALGNLTL | 705 |
| SCN7A | VFHGLIELCLANVA-----GMALLRLFRML>R<IFKLGKYWPTFQILMWSLSNSWVALKDLVL | 632 |
| SCN8A | VSLSLMELSLADVE-----GLSVLRSFRLL>R<VFKLAKSWPTLNMLIKIIGNSVGALGNLTL | 880 |
| SCN9A | VTLSLVELFLADVE-----GLSVLRSFRLL>R<VFKLAKSWPTLNMLIKIIGNSVGALGNLTL | 860 |
| SCN10A | VTVSLLELGVAKKG-----SLSVLRSFRLL>R<VFKLAKSWPTLNTLIKIIGNSVGALGNLTI | 792 |
| SCN11A | ALLSFADVMNCVLQKR---SWPFLRSFRVL>R<VFKLAKSWPTLNTLIKIIGNSVGALGSLTV | 706 |
| CACNA1A | IIGSIFEVIWAVIKPGTSFGISVLRALRLL>R<IFKVTKYWASLRNLVVSLLNSMKSIISLLF | 619 |
| CACNA1B | IVGSVFEVVWAAIKPGSSFGISVLRALRLL>R<IFKVTKYWSSLRNLVVSLLNSMKSIISLLF | 615 |
| CACNA1C | VCGGILETILVETKIMSPLGISVLRCVRLL>R<IFKITRYWNSLSNLVASLLNSVRSIASLLL | 656 |
| CACNA1D | VCGGITETILVELEIMSPLGISVFRCVRLL>R<IFKVTRHWTSLSNLVASLLNSMKSIASLLL | 675 |
| CACNA1E | TVGSIFEVVWAIFRPGTSFGISVLRALRLL>R<IFKITKYWASLRNLVVSLMSSMKSIISLLF | 608 |
| CACNA1F | VCGGILETTLVEVGAMQPLGISVLRCVRLL>R<IFKVTRHWASLSNLVASLLNSMKSIASLLL | 661 |
| CACNA1G | VVISVWEIVGQQGG-----GLSVLRTFRLM>R<VLKLVRFLPALQRQLVVLMKTMDNVATFCM | 870 |
| CACNA1H | VVISVWEIVGQADG-----GLSVLRTFRLL>R<VLKLVRFLPALRRQLVVLVKTMDNVATFCT | 920 |
| CACNA1I | VIISIWEIVGQADG-----GLSVLRTFRLL>R<VLKLVRFMPALRRQLVVLMKTMDNVATFCM | 767 |
| CACNA1S | VCSGILEILLVESGAMTPLGISVLRCIRLL>R<IFKITKYWTSLSNLVASLLNSIRSIASLLL | 564 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R814Q | c.2441G>A | Inherited Arrhythmia | BrS | rs199473584 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | Homozygous SCN5A mutation in Brugada syndrome with monomorphic ventricular tachycardia and structural heart abnormalities. Europace. 2007 9(6):391-7. 17442746 | ||
| p.R814W | c.2440C>T | Cardiomyopathy | DCM | rs199473161 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Cardiomyopathy | DCM | Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA. 2005 293(4):447-54. 15671429 | ||
| Cardiomyopathy | DCM | Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res. 2008 102(3):364-71. 18048769 | |||
| Cardiomyopathy | DCM | Novel SCN5A mutation in amiodarone-responsive multifocal ventricular ectopy-associated cardiomyopathy. Heart Rhythm. 2014 11(8):1446-53. doi: 10.1016/j.hrthm.2014.04.042. 24815523 | |||
| Cardiomyopathy | DCM | Mutations in the Voltage Sensors of Domains I and II of Nav1.5 that are Associated with Arrhythmias and Dilated Cardiomyopathy Generate Gating Pore Currents. Front Pharmacol. 2015 6:301. doi: 10.3389/fphar.2015.00301. eCollection 26733869 | |||