No paralogue variants have been mapped to residue 446 for SCN5A.
| SCN5A | EK-EKRFQEAMEMLKK------------EH>E<ALTIRGVDTVS------------------- | 457 |
| SCN1A | QK-EAEFQQMIEQLKK------------QQ>E<AAQQAATATAS----EHSREPSAAGRL--- | 479 |
| SCN2A | QK-EAEFQQMLEQLKK------------QQ>E<EAQAAAAAASA-----ESRDFSGAGGIGVF | 483 |
| SCN3A | QK-EAEFQQMLEQLKK------------QQ>E<EAQAVAAASAA------SRDFSGIGGLGEL | 481 |
| SCN4A | EK-EEEFQQMLEKFKK------------HQ>E<ELEKAKAAQAL------------------- | 491 |
| SCN7A | KI-EPKFQQTGKELQE------------GN>E<TDEAK------------------------- | 432 |
| SCN8A | QK-EAEFKAMLEQLKK------------QQ>E<EAQAAAMATSAGTVSEDAIEEEGEEGG-GS | 473 |
| SCN9A | QK-ELEFQQMLDRLKK------------EQ>E<EAEAIAAAAAE----YTSIRRSRIMGL--- | 458 |
| SCN10A | AK-EKKFQEALEMLRK------------EQ>E<VLAALGIDTTS------------------- | 441 |
| SCN11A | AK-EKMFQEAQQLLKE------------EK>E<ALVAMGIDRSS------------------- | 444 |
| CACNA1A | FLKLRRQQQIERELNG------------YM>E<WISKA-EE-----------------VILAE | 406 |
| CACNA1B | FLKLRRQQQIERELNG------------YL>E<WIFKA-EE-----------------VMLAE | 402 |
| CACNA1C | FQKLREKQQLEEDLKG------------YL>D<WITQA-ED-----------------IDPEN | 451 |
| CACNA1D | FQKLREKQQLEEDLKG------------YL>D<WITQA-ED-----------------IDPEN | 452 |
| CACNA1E | FMKLRRQQQIERELNG------------YR>A<WIDKA-EE-----------------VMLAE | 397 |
| CACNA1F | FQKQREKQQMEEDLRG------------YL>D<WITQA-EE-----------------LDMED | 418 |
| CACNA1G | EQRVRFLSNASTLASFSEPGSCYEELLKYL>V<YILRKAAR-------------RLAQVSRA- | 457 |
| CACNA1H | EQRARHLSNDSTLASFSEPGSCYEELLKYV>G<HIFRKVKR-------------RSLRLYARW | 482 |
| CACNA1I | EQRQRYLS-SSTVASYAEPGDCYEEIFQYV>C<HILRKAKR-------------RALGLYQAL | 460 |
| CACNA1S | FQKLREKQQLDEDLRG------------YM>S<WITQG-EV-----------------MDVED | 380 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.E446K | c.1336G>A | Cardiomyopathy | DCM | rs199473339 | SIFT: deleterious Polyphen: possibly damaging |
| Reports | Cardiomyopathy | DCM | SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism. J Am Coll Cardiol. 2011 57(21):2160-8. 21596231 | ||
| Unknown | New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. Eur J Hum Genet. 2013 23299917 | ||||
| Cardiomyopathy | DCM | [Dilated cardiomyopathy caused by p.E446K mutation in SCN5A gene]. Kardiologiia. 2014 54(3):92-6. 25102755 | |||
| Unknown | Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381 | ||||
| Unknown | Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510 | ||||