Paralogue Annotation for SCN5A residue 1825

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1825
Reference Amino Acid: L - Leucine
Protein Domain: C-terminus

Paralogue Variants mapped to SCN5A residue 1825

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	L1839V	Dravet syndrome	High	8	24168886
SCN1A	L1839P	Dravet syndrome	High	8	26438699
SCN2A	L1829F	Epileptic encephalopathy, early infantile	High	8	26993267

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	YEIWEKFDPEATQFIEYSVLSDFADALSEP>L<R--IAK--PNQI---SLINMDLPMVSGD-R	1847
SCN1A	YEVWEKFDPDATQFMEFEKLSQFAAALEPP>L<N--LPQ--PNKL---QLIAMDLPMVSGD-R	1861
SCN2A	YEVWEKFDPDATQFIEFAKLSDFADALDPP>L<L--IAK--PNKV---QLIAMDLPMVSGD-R	1851
SCN3A	YEVWEKFDPDATQFIEFSKLSDFAAALDPP>L<L--IAK--PNKV---QLIAMDLPMVSGD-R	1846
SCN4A	YETWEKFDPDATQFIAYSRLSDFVDTLQEP>L<R--IAK--PNKI---KLITLDLPMVPGD-K	1673
SCN7A	FQVWKRFDPDRTQYIDSSKLSDFAAALDPP>L<F--MAK--PNKG---QLIALDLPMAVGD-R	1571
SCN8A	YEIWEKFDPDATQFIEYCKLADFADALEHP>L<R--VPK--PNTI---ELIAMDLPMVSGD-R	1841
SCN9A	YEVWEKFDPDATQFIEFSKLSDFAAALDPP>L<L--IAK--PNKV---QLIAMDLPMVSGD-R	1824
SCN10A	YETWEKFDPEATQFITFSALSDFADTLSGP>L<R--IPK--PNRN---ILIQMDLPLVPGD-K	1797
SCN11A	YEVWEKFDPEATQFIKYSALSDFADALPEP>L<R--VAK--PNKY---QFLVMDLPMVSED-R	1679
CACNA1A	VRVWAEYDPAACGRIHYKDMYSLLRVISPP>L<G--LGKKCPHRVACKRLLRMDLPVADD-NT	1890
CACNA1B	IRVWAEYDPAACGRISYNDMFEMLKHMSPP>L<G--LGKKCPARVAYKRLVRMNMPISNEDMT	1789
CACNA1C	KRIWAEYDPEAKGRIKHLDVVTLLRRIQPP>L<G--FGKLCPHRVACKRLVSMNMPLNSDG-T	1555
CACNA1D	KRIWSEYDPEAKGRIKHLDVVTLLRRIQPP>L<G--FGKLCPHRVACKRLVAMNMPLNSDG-T	1563
CACNA1E	VRVWAEYDRAACGRIHYTEMYEMLTLMSPP>L<G--LGKRCPSKVAYKRLVLMNMPVAED-MT	1802
CACNA1F	KRIWSEYDPGAKGRIKHLDVVALLRRIQPP>L<G--FGKLCPHRVACKRLVAMNMPLNSDG-T	1520
CACNA1G	LELEMKT-LSPQPHSPLGSPF-LWPGVEGP>D<S--PDSPKPGAL---------HPAAHA-RS	1917
CACNA1H	IELEMAQGPGSARRVDADRP---------P>L<P--QESPG--AR--------DAPN------	1913
CACNA1I	LELEMAHGLGPGPRLPTGSPGAPGR---GP>G<GAGGGGDT--EG---GLCRRCYSPAQE-N-	1800
CACNA1S	KAIWAEYDPEAKGRIKHLDVVTLLRRIQPP>L<G--FGKFCPHRVACKRLVGMNMPLNSDG-T	1460
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See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.L1825P	c.5474T>C	Inherited Arrhythmia	LQTS	rs79299226	SIFT: deleterious Polyphen: probably damaging
Reports		Other Cardiac Phenotype		Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation. 2002 106(10):1269-74. 12208804
		Inherited Arrhythmia	LQTS	Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl). 2004 82(3):182-8. 14760488
		Other Cardiac Phenotype		Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome. Circ Arrhythm Electrophysiol. 2009 2(5):511-23. 19843919