| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CACNA1C | N300D | Brugada syndrome | Medium | 7 | 25341504, 25341504 |
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 | DVMVLTVFCLSVFALIGLQLFMGNLRHKCV>R<--------------------NFTALN---G | 289 |
| SCN1A | DVMILTVFCLSVFALIGLQLFMGNLRNKCI>Q<-WP-PTNASLEEH-SI-EKNITVNYN---G | 302 |
| SCN2A | DVMILTVFCLSVFALIGLQLFMGNLRNKCL>Q<-WP-PDNSSFEIN-ITSFFNNSLDGN---G | 304 |
| SCN3A | DVMILTVFCLSVFALIGLQLFMGNLRNKCL>Q<-WP-PSDSAFETN-TTSYFNGTMDSN---G | 303 |
| SCN4A | DVMILTVFCLSVFALVGLQLFMGNLRQKCV>R<-WP-PPFN--DTN-TTWYSNDTWYGN---D | 304 |
| SCN7A | GVIILTLFFLSIFSLIGMGLFMGNLKHKCF>R<-WP-QENE-----------------N---E | 277 |
| SCN8A | DVMILTVFCLSVFALIGLQLFMGNLRNKCV>V<-WP-------------------INFN---E | 290 |
| SCN9A | DVMILTVFCLSVFALIGLQLFMGNLKHKCF>R<-NS-------------------LENN---E | 284 |
| SCN10A | DVTILTIFCLSVFALVGLQLFKGNLKNKCV>K<-N-------------------DMAVN---E | 285 |
| SCN11A | NVIILTFFCLSIFALVGQQLFMGSLNLKCI>S<-R-------------------DCK-N---I | 291 |
| CACNA1A | QIGLLLFFAILIFAIIGLEFYMGKFHTTCF>E<-E-GTD------------DI-----Q---G | 266 |
| CACNA1B | QIGLLLFFAILMFAIIGLEFYMGKFHKACF>P<-N-STD------------A------E---P | 262 |
| CACNA1C | HIALLVLFVIIIYAIIGLELFMGKMHKTCY>N<QEGIAD-------------V----PA---E | 310 |
| CACNA1D | HIALLVLFVIIIYAIIGLELFIGKMHKTCF>F<-A-DSD-------------I----VA---E | 311 |
| CACNA1E | QIGLLLFFAILMFAIIGLEFYSGKLHRACF>M<-N-NSG------------IL----EG---F | 262 |
| CACNA1F | HIALLVLFVIIIYAIIGLELFLGRMHKTCY>F<-L-GSD-------------M----EA---E | 277 |
| CACNA1G | NVLLLCFFVFFIFGIVGVQLWAGLLRNRCF>L<-P-ENFSLPLSVD-LE-RYYQT-ENE---D | 265 |
| CACNA1H | NVLLLCFFVFFIFGIVGVQLWAGLLRNRCF>L<-D-SAFVRNNNLTFLR-PYYQT-EEG---E | 285 |
| CACNA1I | NVLLLCFFVFFIFGIIGVQLWAGLLRNRCF>L<-E-ENFTIQGDVA-LP-PYYQP-EED---D | 263 |
| CACNA1S | HIALLVLFMVIIYAIIGLELFKGKMHKTCY>F<-I-GTD-------------I----VATVEN | 239 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.R282C | c.844C>T | Inherited Arrhythmia | BrS | rs199473082 | 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 | ||
| p.R282H | c.845G>A | Inherited Arrhythmia | BrS | rs199473083 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | BrS | Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 2002 105(11):1342-7. 11901046 | ||
| Inherited Arrhythmia | BrS | Clinical and electrophysiological characteristics of Brugada syndrome caused by a missense mutation in the S5-pore site of SCN5A. J Cardiovasc Electrophysiol. 2005 16(4):378-83. 15828879 | |||
| Inherited Arrhythmia | BrS | A novel strategy using cardiac sodium channel polymorphic fragments to rescue trafficking-deficient SCN5A mutations. Circ Cardiovasc Genet. 2011 4(5):500-9. 21840964 | |||
| Inherited Arrhythmia | BrS | Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. Am J Hum Genet. 2016 98(5):801-17. doi: 10.1016/j.ajhg.2016.02.024. 27153395 | |||