Paralogue Annotation for SCN5A residue 1913

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1913
Reference Amino Acid: R - Arginine
Protein Domain: C-terminus

Paralogue Variants mapped to SCN5A residue 1913

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CACNA1A	R1967Q	Epilepsy, idiopathic	High	8	21703448, 23869231
SCN10A	R1863Q	Brugada syndrome	High	8	25842276
SCN1A	R1927T	Dravet syndrome	High	8	26096185
SCN1A	R1927G	Generalized epilepsy with febrile seizures plus	High	8

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	SYEPITTTLRRKHEEVS----AMVIQRAF->R<RHLLQRS--LKHA-SFLFRQ---------Q	1931
SCN1A	SYQPITTTLKRKQEEVS----AVIIQRAY->R<RHLLKRT--VKQA-SFTYNK---------N	1945
SCN2A	SYEPITTTLKRKQEEVS----AIIIQRAY->R<RYLLKQK--VKKV-SSIYKK---------D	1935
SCN3A	SYEPITTTLKRKQEEVS----AAIIQRNF->R<CYLLKQR--LKNI-SSNYNK---------E	1930
SCN4A	SYEPITTTLKRKHEEVC----AIKIQRAY->R<RHLLQRS--MKQA-SYMYRH---------S	1757
SCN7A	TCEPITTTLKRKQEAVS----ATIIQRAY->K<NYRLRRN--DKNT-SDIHMI---------D	1655
SCN8A	SYEPITTTLRRKQEEVS----AVVLQRAY->R<GHLARRG--FIC------------------	1917
SCN9A	SYEPITTTLKRKQEDVS----ATVIQRAY->R<RYRLRQN--VKNI-SSIYIK---------D	1908
SCN10A	SYEPIATTLRWKQEDIS----ATVIQKAY->R<SYVLHRS--MALS-NTPCVP---------R	1881
SCN11A	LYEPIVTTTKRKEEERG----AAIIQKAF->R<KYMMKVT--KGDQ-G-D--Q----------	1759
CACNA1A	TLDLLVTPHKSTDLTVGKIYAAMMIMEYY->R<QSKAKK--LQAMR-E---EQDRTPLMFQRM	1991
CACNA1B	TLDLLVPPHKPDEMTVGKVYAALMIFDFY->K<QNKTTRDQMQQAPGG---LS----QMGPVS	1889
CACNA1C	LLDQVVPPAGDDEVTVGKFYATFLIQEYF->R<KFKKRKE--QGLV-GK--PS--------QR	1646
CACNA1D	LLDQVVPPAGDDEVTVGKFYATFLIQDYF->R<KFKKRKE--QGLV-GK-YPA--------KN	1655
CACNA1E	MLDLLVPMPKASDLTVGKIYAAMMIMDYY->K<QSKVKKQ--RQQL-E---EQ-KNAPMFQRM	1902
CACNA1F	LLDEVIPPPDEEEVTVGKFYATFLIQDYF->R<KFRRRKE--KGLL-GN-DAA--------PS	1612
CACNA1G	SAFPSAPSLGGSDP-----QIPLAEMEAL->S<LTSEIVS--EPSC-----------------	1996
CACNA1H	-FRPVVPASAPHPR-----PLQEVEMETYG>A<GTPLGSV--ASVH-SP-PAE-SCASLQIPL	1983
CACNA1I	-FHHYSSPAGCKKCHHDKQEVQLAETEAF->S<LNSDRSS--SILL-GD-DLS-LEDPTACPP	1882
CACNA1S	LLDQVIPPIGDDEVTVGKFYATFLIQEHF->R<KFMKRQE--EYY--GY--RP--------KK	1550
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.R1913H	c.5738G>A	Inherited Arrhythmia	LQTS	rs199473327	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005 294(23):2975-80. 16414944