| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CACNA1A | R195K | Hemiplegic migraine | High | 9 | 11439943 |
| SCN11A | R222S | Episodic pain syndrome | High | 9 | 27224030 |
| SCN11A | R222H | Episodic pain syndrome | High | 9 | 27224030 |
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 | VSENIKLG-----------------NLSAL>R<TFRVLRALKTISVIPGLKTIVGALIQSVKK | 249 |
| SCN1A | VTEFVDLG-----------------NVSAL>R<TFRVLRALKTISVIPGLKTIVGALIQSVKK | 246 |
| SCN2A | VTEFVDLG-----------------NVSAL>R<TFRVLRALKTISVIPGLKTIVGALIQSVKK | 247 |
| SCN3A | VTEFVDLG-----------------NVSAL>R<TFRVLRALKTISVIPGLKTIVGALIQSVKK | 246 |
| SCN4A | LTEFVDLG-----------------NISAL>R<TFRVLRALKTITVIPGLKTIVGALIQSVKK | 249 |
| SCN7A | IIRYSPLD-----------------FIPTL>Q<TARTLRILKIIPLNQGLKSLVGVLIHCLKQ | 236 |
| SCN8A | ITEFVNLG-----------------NVSAL>R<TFRVLRALKTISVIPGLKTIVGALIQSVKK | 250 |
| SCN9A | LTEFVNLG-----------------NVSAL>R<TFRVLRALKTISVIPGLKTIVGALIQSVKK | 244 |
| SCN10A | VGTAIDLR-----------------GISGL>R<TFRVLRALKTVSVIPGLKVIVGALIHSVKK | 245 |
| SCN11A | VSYIPGIT----------------IKLLPL>R<TFRVFRALKAISVVSRLKVIVGALLRSVKK | 252 |
| CACNA1A | LATVGTEF-----------------DLRTL>R<AVRVLRPLKLVSGIPSLQVVLKSIMKAMIP | 225 |
| CACNA1B | LATAGTDF-----------------DLRTL>R<AVRVLRPLKLVSGIPSLQVVLKSIMKAMVP | 222 |
| CACNA1C | FSAILEQATKA-DGANALGGKGAGFDVKAL>R<AFRVLRPLRLVSGVPSLQVVLNSIIKAMVP | 267 |
| CACNA1D | FSVILEQLTKETEGGNHSSGKSGGFDVKAL>R<AFRVLRPLRLVSGVPSLQVVLNSIIKAMVP | 270 |
| CACNA1E | LATAGTHFN-------------THVDLRTL>R<AVRVLRPLKLVSGIPSLQIVLKSIMKAMVP | 220 |
| CACNA1F | FSVLLEQGPGRPGDAPHTGGKPGGFDVKAL>R<AFRVLRPLRLVSGVPSLHIVLNSIMKALVP | 236 |
| CACNA1G | LEYSLDLQ---------------NVSFSAV>R<TVRVLRPLRAINRVPSMRILVTLLLDTLPM | 210 |
| CACNA1H | MEYSLDGH---------------NVSLSAI>R<TVRVLRPLRAINRVPSMRILVTLLLDTLPM | 229 |
| CACNA1I | VEYSLDLQ---------------NINLSAI>R<TVRVLRPLKAINRVPSMRILVNLLLDTLPM | 208 |
| CACNA1S | FTVILEQVNVIQSHTAPMSSKGAGLDVKAL>R<AFRVLRPLRLVSGVPSLQVVLNSIFKAMLP | 195 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R219H | c.656G>A | Cardiomyopathy | DCM | SIFT: deleterious Polyphen: probably damaging | |
| Reports | Cardiomyopathy | DCM | A proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype. PLoS One. 2012 7(5):e38331. 22675453 | ||
| Other Cardiac Phenotype | Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics. Circ Arrhythm Electrophysiol. 2014 7(3):511-7. doi: 10.1161/CIRCEP.113.001340. 24762805 | ||||
| Other Cardiac Phenotype | Familial Paralysis of the Atrium Due to a Mutation in SCN5A. Rev Esp Cardiol (Engl Ed). 2015 68(10):904-6. doi: 10.1016/j.rec.2015.06.014. 26304136 | ||||
| p.R219C | c.655C>T | Putative Benign | SIFT: Polyphen: | ||