| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R931C | Myoclonic epilepsy of infancy | High | 8 | 12083760 |
| SCN9A | R896Q | Congenital indifference to pain | High | 8 | 20635406 |
| SCN1A | R931H | Epilepsy ? | High | 8 | 21248271, 21719429 |
| SCN1A | R931P | Dravet syndrome | High | 8 | 24168886 |
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 | GMQLFGKNYSEL-RDS----D-SG---LLP>R<WHMMDFFHAFLIIFRILCGE-WIETMWDCM | 907 |
| SCN1A | GMQLFGKSYKDC-VCK----I-AS-DCQLP>R<WHMNDFFHSFLIVFRVLCGE-WIETMWDCM | 960 |
| SCN2A | GMQLFGKSYKEC-VCK----I-SN-DCELP>R<WHMHDFFHSFLIVFRVLCGE-WIETMWDCM | 951 |
| SCN3A | GMQLFGKSYKEC-VCK----I-ND-DCTLP>R<WHMNDFFHSFLIVFRVLCGE-WIETMWDCM | 952 |
| SCN4A | GMQLFGKSYKEC-VCK----I-AL-DCNLP>R<WHMHDFFHSFLIVFRILCGE-WIETMWDCM | 770 |
| SCN7A | GMKLFGKNYEEF-VCH----I-DK-DCQLP>R<WHMHDFFHSFLNVFRILCGE-WVETLWDCM | 697 |
| SCN8A | GMQLFGKSYKEC-VCK----I-NQ-DCELP>R<WHMHDFFHSFLIVFRVLCGE-WIETMWDCM | 945 |
| SCN9A | GMQLFGKSYKEC-VCK----I-ND-DCTLP>R<WHMNDFFHSFLIVFRVLCGE-WIETMWDCM | 925 |
| SCN10A | GKQLLGENYRNN-RKN----I-SAPHEDWP>R<WHMHDFFHSFLIVFRILCGE-WIENMWACM | 858 |
| SCN11A | GMQLFGRSFNSQ-KSPKLCNPTGPTVSCLR>H<WHMGDFWHSFLVVFRILCGE-WIENMWECM | 777 |
| CACNA1A | GMQLFGGQFNFD-E------------G-TP>P<TNFDTFPAAIMTVFQILTGEDWNEVMYDGI | 678 |
| CACNA1B | GMQLFGGQFNFQ-D------------E-TP>T<TNFDTFPAAILTVFQILTGEDWNAVMYHGI | 674 |
| CACNA1C | GMQLFGGKFNFD-E------------MQTR>R<STFDNFPQSLLTVFQILTGEDWNSVMYDGI | 716 |
| CACNA1D | GMQLFGGKFNFD-E------------TQTK>R<STFDNFPQALLTVFQILTGEDWNAVMYDGI | 735 |
| CACNA1E | GMQLFGGRFNFN-D------------G-TP>S<ANFDTFPAAIMTVFQILTGEDWNEVMYNGI | 667 |
| CACNA1F | GMQLFGGKFNFD-Q------------THTK>R<STFDTFPQALLTVFQILTGEDWNVVMYDGI | 721 |
| CACNA1G | GMHLFGCKFASER---------DG-DTLPD>R<KNFDSLLWAIVTVFQILTQEDWNKVLYNGM | 933 |
| CACNA1H | GMHLFGCKFSLKTD--------TG-DTVPD>R<KNFDSLLWAIVTVFQILTQEDWNVVLYNGM | 984 |
| CACNA1I | GMHIFGCKFSLRTD--------TG-DTVPD>R<KNFDSLLWAIVTVFQILTQEDWNVVLYNGM | 831 |
| CACNA1S | GMQLFGGRYDFE-D------------TEVR>R<SNFDNFPQALISVFQVLTGEDWTSMMYNGI | 624 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R878C | c.2632C>T | Inherited Arrhythmia | BrS | rs199473168 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel. Acta Physiol (Oxf). 2008 194(4):311-23. 18616619 | ||
| 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 | Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome. PLoS One. 2010 5(6):e10985. 20539757 | |||
| Inherited Arrhythmia | BrS | Gene symbol: SCN5A. Disease: Brugada syndrome. Hum Genet. 2008 123(5):542. 20960617 | |||
| 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.R878H | c.2633G>A | Inherited Arrhythmia | BrS | rs199473587 | 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 | |||