| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| CACNA1D | G407R | Autism | High | 9 | 22542183, 25620733 |
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 CACNA1C.
| CACNA1C | VGRDWPWIYFVTLIIIGSFFVLNLVLGVLS>G<EFSKEREKAKARGDFQKLREKQQLEEDLKG | 436 |
| CACNA1A | SGNTWNWLYFIPLIIIGSFFMLNLVLGVLS>G<EFAKERERVENRRAFLKLRRQQQIERELNG | 391 |
| CACNA1B | AGNTWNWLYFIPLIIIGSFFMLNLVLGVLS>G<EFAKERERVENRRAFLKLRRQQQIERELNG | 387 |
| CACNA1D | IGWEWPWVYFVSLIILGSFFVLNLVLGVLS>G<EFSKEREKAKARGDFQKLREKQQLEEDLKG | 437 |
| CACNA1E | LGATWNWLYFIPLIIIGSFFVLNLVLGVLS>G<EFAKERERVENRRAFMKLRRQQQIERELNG | 382 |
| CACNA1F | MGYELPWVYFVSLVIFGSFFVLNLVLGVLS>G<EFSKEREKAKARGDFQKQREKQQMEEDLRG | 403 |
| CACNA1G | HSF-YNFIYFILLIIVGSFFMINLCLVVIA>T<QFSETKQRESQLMREQRVRFLSNASTLASF | 426 |
| CACNA1H | HSF-YNFIYFILLIIVGSFFMINLCLVVIA>T<QFSETKQRESQLMREQRARHLSNDSTLASF | 450 |
| CACNA1I | HSF-YNFIYFILLIIVGSFFMINLCLVVIA>T<QFSETKQREHRLMLEQRQRYLS-SSTVASY | 428 |
| CACNA1S | IGNEWPWIYFVTLILLGSFFILNLVLGVLS>G<EFTKEREKAKSRGTFQKLREKQQLDEDLRG | 365 |
| SCN10A | SGKIY-MIFFVLVIFLGSFYLVNLILAVVT>M<AYEEQNQATTDEIEAK-EKKFQEALEMLRK | 427 |
| SCN11A | TGLYS-VFFFIVVIFLGSFYLINLTLAVVT>M<AYEEQNKNVAAEIEAK-EKMFQEAQQLLKE | 430 |
| SCN1A | AGKTY-MIFFVLVIFLGSFYLINLILAVVA>M<AYEEQNQATLEEAEQK-EAEFQQMIEQLKK | 453 |
| SCN2A | AGKTY-MIFFVLVIFLGSFYLINLILAVVA>M<AYEEQNQATLEEAEQK-EAEFQQMLEQLKK | 455 |
| SCN3A | AGKTY-MIFFVLVIFLGSFYLVNLILAVVA>M<AYEEQNQATLEEAEQK-EAEFQQMLEQLKK | 454 |
| SCN4A | AGKTY-MIFFVVIIFLGSFYLINLILAVVA>M<AYAEQNEATLAEDKEK-EEEFQQMLEKFKK | 477 |
| SCN5A | AGKIY-MIFFMLVIFLGSFYLVNLILAVVA>M<AYEEQNQATIAETEEK-EKRFQEAMEMLKK | 443 |
| SCN7A | SGKVY-MIFFVVVSFLFSFYMASLFLGILA>M<AYEEEKQRVGEISKKI-EPKFQQTGKELQE | 424 |
| SCN8A | AGKTY-MIFFVLVIFVGSFYLVNLILAVVA>M<AYEEQNQATLEEAEQK-EAEFKAMLEQLKK | 441 |
| SCN9A | AGKTY-MIFFVVVIFLGSFYLINLILAVVA>M<AYEEQNQANIEEAKQK-ELEFQQMLDRLKK | 432 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.G406R | c.1216G>A | Inherited Arrhythmia | LQTS | rs79891110 | SIFT: deleterious Polyphen: probably damaging |
| Reports | Inherited Arrhythmia | LQTS | Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004 119(1):19-31. 15454078 | ||
| Inherited Arrhythmia | LQTS | Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A. 2005 discussion 8086-8. 15863612 | |||
| Inherited Arrhythmia | LQTS | Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007 115(4):442-9. 17224476 | |||
| Inherited Arrhythmia | LQTS | The Timothy syndrome mutation of cardiac CaV1.2 (L-type) channels: multiple altered gating mechanisms and pharmacological restoration of inactivation. J Physiol. 2009 587(Pt 3):551-65. 19074970 | |||
| Inherited Arrhythmia | LQTS | Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci U S A. 2011 108(37):15432-7. 21878566 | |||
| Inherited Arrhythmia | LQTS | Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome. Pediatrics. 2013 131(6):e1991-5. doi: 10.1542/peds.2012-2941. 23690510 | |||
| Inherited Arrhythmia | LQTS | Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Nat Neurosci. 2013 16(2):201-9. doi: 10.1038/nn.3307. 23313911 | |||
| Inherited Arrhythmia | LQTS | Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory. Genet Test Mol Biomarkers. 2013 17(7):553-61. doi: 10.1089/gtmb.2012.0118. 23631430 | |||
| Inherited Arrhythmia | LQTS | Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome. J Korean Med Sci. 2013 28(5):788-91. doi: 10.3346/jkms.2013.28.5.788. 23678275 | |||
| Inherited Arrhythmia | LQTS | Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. Am J Med Genet A. 2011 155A(10):2578-83. doi: 10.1002/ajmg.a.34223. 21910241 | |||
| Inherited Arrhythmia | LQTS | Inhibition of late sodium current by mexiletine: a novel pharmotherapeutical approach in timothy syndrome. Circ Arrhythm Electrophysiol. 2013 6(3):614-22. doi: 10.1161/CIRCEP.113.000092. 23580742 | |||