| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| SCN1A | R101W | Myoclonic epilepsy of infancy | High | 7 | 17347258, 27236449 |
| SCN1A | R101Q | Myoclonic epilepsy of infancy | High | 7 | 14738421, 23195492, 23808377, 23158734, 24328833, 25885068 |
| SCN4A | R104H | Myopathy, congenital | High | 7 | 26700687 |
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 | IGEPLEDLDPFYSTQK-TFI-VLNKGKTIF>R<FSATNALYVLSPFHPIRRAAVKILVHSLFN | 134 |
| SCN1A | VSEPLEDLDPYYINKK-TFI-VLNKGKAIF>R<FSATSALYILTPFNPLRKIAIKILVHSLFS | 131 |
| SCN2A | VSVPLEDLDPYYINKK-TFI-VLNKGKAIS>R<FSATPALYILTPFNPIRKLAIKILVHSLFN | 132 |
| SCN3A | VSEPLEDLDPYYINKK-TFI-VMNKGKAIF>R<FSATSALYILTPLNPVRKIAIKILVHSLFS | 131 |
| SCN4A | IGIPLEDLDPYYSNKK-TFI-VLNKGKAIF>R<FSATPALYLLSPFSVVRRGAIKVLIHALFS | 134 |
| SCN7A | VSEPLEDVDPYYYKKKNTFI-VLNKNRTIF>R<FNAASILCTLSPFNCIRRTTIKVLVHPFFQ | 121 |
| SCN8A | VAVPLEDFDPYYLTQK-TFV-VLNRGKTLF>R<FSATPALYILSPFNLIRRIAIKILIHSVFS | 135 |
| SCN9A | VSEPLEDLDPYYADKK-TFI-VLNKGKTIF>R<FNATPALYMLSPFSPLRRISIKILVHSLFS | 129 |
| SCN10A | IGEPLEDLDPFYSTHR-TFM-VLNKGRTIS>R<FSATRALWLFSPFNLIRRTAIKVSVHSWFS | 133 |
| SCN11A | IGKPLEDLDPFYRNHK-TFM-VLNRKRTIY>R<FSAKHALFIFGPFNSIRSLAIRVSVHSLFS | 132 |
| CACNA1A | ---QRMYKQSMAQRARTMAL-YNPIPVRQN>C<LTVNRSLFLFSEDNVVRKYAKKITEWPPFE | 101 |
| CACNA1B | ---RVLYKQSIAQRARTMAL-YNPIPVKQN>C<FTVNRSLFVFSEDNVVRKYAKRITEWPPFE | 98 |
| CACNA1C | GNATISTVSST-QRKRQQYG-KPKKQGSTT>A<TRPPRALLCLTLKNPIRRACISIVEWKPFE | 127 |
| CACNA1D | STSAPPPVGSLSQRKRQQYA-KSKKQGNSS>N<SRPARALFCLSLNNPIRRACISIVEWKPFD | 129 |
| CACNA1E | ---AAAYKQTKAQRARTMAL-YNPIPVRQN>C<FTVNRSLFIFGEDNIVRKYAKKLIDWPPFE | 92 |
| CACNA1F | EGESSGASGLGTPKRRNQHS-KHKTVAVAS>A<QRSPRALFCLTLANPLRRSCISIVEWKPFD | 95 |
| CACNA1G | --PGSA-------EKDPG-SADSEAEGLPY>P<ALAPVVFFYLSQDSRPRSWCLRTVCNPWFE | 84 |
| CACNA1H | --P-AA-------ERGAELG-ADEEQRVPY>P<ALAATVFFCLGQTTRPRSWCLRLVCNPWFE | 103 |
| CACNA1I | --SPPG-------LEEPL-D-G-ADPHVPH>P<DLAPIAFFCLRQTTSPRNWCIKMVCNPWFE | 82 |
| CACNA1S | ---------SSPQDEGLRKK-QPKKPVPEI>L<PRPPRALFCLTLENPLRKACISIVEWKPFE | 54 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R104G | c.310C>G | Inherited Arrhythmia | LQTS | rs199473055 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm. 2009 6(9):1297-303. 19716085 | ||
| p.R104Q | c.311G>A | Inherited Arrhythmia | BrS | rs199473554 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | Genetic analysis of Brugada syndrome in Israel: two novel mutations and possible genetic heterogeneity. Genet Test. 2001 5(4):331-4. 11960580 | ||
| 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 | Characterization of N-terminally mutated cardiac Na(+) channels associated with long QT syndrome 3 and Brugada syndrome. Front Physiol. 2013 4:153. doi: 10.3389/fphys.2013.00153. eCollection 23805106 | |||
| 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.R104W | c.310C>T | Inherited Arrhythmia | BrS | rs199473055 | 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 | 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 | |||