Paralogue Annotation for SCN5A residue 1278

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1278
Reference Amino Acid: I - Isoleucine
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1278

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN10A	I1225T	Brugada syndrome	High	9	24998131, 25650408

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	LEMLLKWVAYGF----KKYFTNAWCWLDFL>I<VDVSLVSLVAN-T----LGFAEMGPIKSLR	1303
SCN1A	LEMLLKWVAYGY----QTYFTNAWCWLDFL>I<VDVSLVSLTAN-A----LGYSELGAIKSLR	1316
SCN2A	LEMLLKWVAYGF----QVYFTNAWCWLDFL>I<VDVSLVSLTAN-A----LGYSELGAIKSLR	1306
SCN3A	LEMLLKWVAYGF----QTYFTNAWCWLDFL>I<VDVSLVSLVAN-A----LGYSELGAIKSLR	1304
SCN4A	MEMLLKWVAYGF----KVYFTNAWCWLDFL>I<VDVSIISLVAN-W----LGYSELGPIKSLR	1129
SCN7A	LEMLLKWMAYGF----KAYFSNGWYRLDFV>V<VIVFCLSLIGK-T----RE--E---LKPLI	1027
SCN8A	LEMLLKWTAYGF----VKFFTNAWCWLDFL>I<VAVSLVSLIAN-A----LGYSELGAIKSLR	1296
SCN9A	LEMLLKWIAYGY----KTYFTNAWCWLDFL>I<VDVSLVTLVAN-T----LGYSDLGPIKSLR	1279
SCN10A	FEMLLKWVAYGF----KKYFTNAWCWLDFL>I<VNISLISLTAK-I----LEYSEVAPIKALR	1250
SCN11A	LEMVLKWVAFGF----GKYFTSAWCCLDFI>I<VIVSVTTLI---------N---LMELKSFR	1147
CACNA1A	FEMVIKMIDLGLVLHQGAYFRDLWNILDFI>V<VSGALVAFAFTGN----SKGKDINTIKSLR	1346
CACNA1B	FEMVIKMIDLGLLLHPGAYFRDLWNILDFI>V<VSGALVAFAFS-G----SKGKDINTIKSLR	1252
CACNA1C	IEIALKMTAYGAFLHKGSFCRNYFNILDLL>V<VSVSLISF----G----IQSSAINVVKILR	998
CACNA1D	VEILLKMTTFGAFLHKGAFCRNYFNLLDML>V<VGVSLVSF----G----IQSSAISVVKILR	1004
CACNA1E	FEMVIKMIDQGLILQDGSYFRDLWNILDFV>V<VVGALVAFALANA-LGTNKGRDIKTIKSLR	1258
CACNA1F	VEILLKMTVFGAFLHRGSFCRSWFNMLDLL>V<VSVSLISF----G----IHSSAISVVKILR	969
CACNA1G	AEMTVKVVALGWCFGEQAYLRSSWNVLDGL>L<VLISVIDILVS-MVSD-SGTKILGMLRVLR	1381
CACNA1H	AEMMVKVVALGLLSGEHAYLQSSWNLLDGL>L<VLVSLVDIVVA-MASA-GGAKILGVLRVLR	1399
CACNA1I	GEMTLKVVSLGLYFGEQAYLRSSWNVLDGF>L<VFVSIIDIVVS-LASA-GGAKILGVLRVLR	1275
CACNA1S	VEIVLKMTTYGAFLHKGSFCRNYFNMLDLL>V<VAVSLISM----G----LESSAISVVKILR	897
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.I1278N	c.3833T>A	Inherited Arrhythmia	LQTS	rs199473215	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	LQTS	Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300