Paralogue Annotation for CACNA1C residue 1475

Residue details

Gene: CACNA1C
Reference Sequences: LRG: LRG_334, Ensembl variant: ENST00000399655 / ENSP00000382563
Amino Acid Position: 1475
Reference Amino Acid: I - Isoleucine
Protein Domain: TM domain 4

Paralogue Variants mapped to CACNA1C residue 1475

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CACNA1A	I1811L	Hemiplegic migraine and episodic ataxia 2	High	9	8898206, 10024348, 9488686

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	-CGS-SFAVFYFISFYMLCAFLIINLFVAV>I<MDNFDYLTRDWSI-LGPHHLDEFKRIWAEY	1504
CACNA1A	ECGN-EFAYFYFVSFIFLCSFLMLNLFVAV>I<MDNFEYLTRDSSI-LGPHHLDEYVRVWAEY	1839
CACNA1B	ECGS-DFAYFYFVSFIFLCSFLMLNLFVAV>I<MDNFEYLTRDSSI-LGPHHLDEFIRVWAEY	1737
CACNA1D	-CGS-NFAIVYFISFYMLCAFLIINLFVAV>I<MDNFDYLTRDWSI-LGPHHLDEFKRIWSEY	1512
CACNA1E	RCGT-DLAYVYFVSFIFFCSFLMLNLFVAV>I<MDNFEYLTRDSSI-LGPHHLDEFVRVWAEY	1751
CACNA1F	-CGS-NFAIAYFISFFMLCAFLIINLFVAV>I<MDNFDYLTRDWSI-LGPHHLDEFKRIWSEY	1469
CACNA1G	-YNT-VISPIYFVSFVLTAQFVLVNVVIAV>L<MKHLEESNKEAKE---EAELEAELELEMKT	1877
CACNA1H	-YLP-ALSPVYFVTFVLVAQFVLVNVVVAV>L<MKHLEESNKEARE---DAELDAEIELEMAQ	1886
CACNA1I	-SLQ-FVSPLYFVSFVLTAQFVLINVVVAV>L<MKHLDDSNKEAQE---DAEMDAELELEMAH	1756
CACNA1S	-CGT-NFAYYYFISFYMLCAFLVINLFVAV>I<MDNFDYLTRDWSI-LGPHHLDEFKAIWAEY	1409
SCN10A	-CGSPAVGIIFFTTYIIISFLIMVNMYIAV>I<LENFNVATEESTEPLSEDDFDMFYETWEKF	1751
SCN11A	-CHLPGIATSYFVSYIIISFLIVVNMYIAV>I<LENFNTATEESEDPLGEDDFDIFYEVWEKF	1633
SCN1A	-CGNPSVGIFFFVSYIIISFLVVVNMYIAV>I<LENFSVATEESAEPLSEDDFEMFYEVWEKF	1815
SCN2A	-CGNPSVGIFFFVSYIIISFLVVVNMYIAV>I<LENFSVATEESAEPLSEDDFEMFYEVWEKF	1805
SCN3A	-CGNPSVGIFFFVSYIIISFLVVVNMYIAV>I<LENFSVATEESAEPLSEDDFEMFYEVWEKF	1800
SCN4A	-CGNPSIGICFFCSYIIISFLIVVNMYIAI>I<LENFNVATEESSEPLGEDDFEMFYETWEKF	1627
SCN5A	-CGSPAVGILFFTTYIIISFLIVVNMYIAI>I<LENFSVATEESTEPLSEDDFDMFYEIWEKF	1801
SCN7A	-CGNPSVGIFYFVSYILISWLIIVNMYIVV>V<MEFLNIASKKKNKTLSEDDFRKFFQVWKRF	1525
SCN8A	-CGNPSVGIFFFVSYIIISFLIVVNMYIAI>I<LENFSVATEESADPLSEDDFETFYEIWEKF	1795
SCN9A	-CGNPSVGIFYFVSYIIISFLVVVNMYIAV>I<LENFSVATEESTEPLSEDDFEMFYEVWEKF	1778
cons	> <

See full Alignment of Paralogues

Known Variants in CACNA1C

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.I1475M	c.4425C>G	Inherited Arrhythmia	LQTS		SIFT: Polyphen:
Reports		Inherited Arrhythmia	LQTS	Gain-of-function mutations in the calcium channel CACNA1C (Cav1.2) cause non-syndromic long-QT but not Timothy syndrome. J Mol Cell Cardiol. 2015 80:186-95. doi: 10.1016/j.yjmcc.2015.01.002. 25633834