Paralogue Annotation for CACNA1C residue 406

Residue details

Gene: CACNA1C
Reference Sequences: LRG: LRG_334, Ensembl variant: ENST00000399655 / ENSP00000382563
Amino Acid Position: 406
Reference Amino Acid: G - Glycine
Protein Domain: Interdomain Linker I-II


Paralogue Variants mapped to CACNA1C residue 406

ParalogueVariantAssociated DiseaseMapping QualityConsensusPubmed
CACNA1DG407RAutismHigh9 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.



CACNA1CVGRDWPWIYFVTLIIIGSFFVLNLVLGVLS>G<EFSKEREKAKARGDFQKLREKQQLEEDLKG436
CACNA1ASGNTWNWLYFIPLIIIGSFFMLNLVLGVLS>G<EFAKERERVENRRAFLKLRRQQQIERELNG391
CACNA1BAGNTWNWLYFIPLIIIGSFFMLNLVLGVLS>G<EFAKERERVENRRAFLKLRRQQQIERELNG387
CACNA1DIGWEWPWVYFVSLIILGSFFVLNLVLGVLS>G<EFSKEREKAKARGDFQKLREKQQLEEDLKG437
CACNA1ELGATWNWLYFIPLIIIGSFFVLNLVLGVLS>G<EFAKERERVENRRAFMKLRRQQQIERELNG382
CACNA1FMGYELPWVYFVSLVIFGSFFVLNLVLGVLS>G<EFSKEREKAKARGDFQKQREKQQMEEDLRG403
CACNA1GHSF-YNFIYFILLIIVGSFFMINLCLVVIA>T<QFSETKQRESQLMREQRVRFLSNASTLASF426
CACNA1HHSF-YNFIYFILLIIVGSFFMINLCLVVIA>T<QFSETKQRESQLMREQRARHLSNDSTLASF450
CACNA1IHSF-YNFIYFILLIIVGSFFMINLCLVVIA>T<QFSETKQREHRLMLEQRQRYLS-SSTVASY428
CACNA1SIGNEWPWIYFVTLILLGSFFILNLVLGVLS>G<EFTKEREKAKSRGTFQKLREKQQLDEDLRG365
SCN10ASGKIY-MIFFVLVIFLGSFYLVNLILAVVT>M<AYEEQNQATTDEIEAK-EKKFQEALEMLRK427
SCN11ATGLYS-VFFFIVVIFLGSFYLINLTLAVVT>M<AYEEQNKNVAAEIEAK-EKMFQEAQQLLKE430
SCN1AAGKTY-MIFFVLVIFLGSFYLINLILAVVA>M<AYEEQNQATLEEAEQK-EAEFQQMIEQLKK453
SCN2AAGKTY-MIFFVLVIFLGSFYLINLILAVVA>M<AYEEQNQATLEEAEQK-EAEFQQMLEQLKK455
SCN3AAGKTY-MIFFVLVIFLGSFYLVNLILAVVA>M<AYEEQNQATLEEAEQK-EAEFQQMLEQLKK454
SCN4AAGKTY-MIFFVVIIFLGSFYLINLILAVVA>M<AYAEQNEATLAEDKEK-EEEFQQMLEKFKK477
SCN5AAGKIY-MIFFMLVIFLGSFYLVNLILAVVA>M<AYEEQNQATIAETEEK-EKRFQEAMEMLKK443
SCN7ASGKVY-MIFFVVVSFLFSFYMASLFLGILA>M<AYEEEKQRVGEISKKI-EPKFQQTGKELQE424
SCN8AAGKTY-MIFFVLVIFVGSFYLVNLILAVVA>M<AYEEQNQATLEEAEQK-EAEFKAMLEQLKK441
SCN9AAGKTY-MIFFVVVIFLGSFYLINLILAVVA>M<AYEEQNQANIEEAKQK-ELEFQQMLDRLKK432
cons                              > <                              

See full Alignment of Paralogues


Known Variants in CACNA1C

ProteinCDSDisease ClassificationDiseasedbSNP linksEffect Prediction
p.G406Rc.1216G>A Inherited ArrhythmiaLQTSrs79891110SIFT: deleterious
Polyphen: probably damaging
ReportsInherited ArrhythmiaLQTS Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004 119(1):19-31. 15454078
Inherited ArrhythmiaLQTS Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A. 2005 discussion 8086-8. 15863612
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci U S A. 2011 108(37):15432-7. 21878566
Inherited ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS 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 ArrhythmiaLQTS 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