Paralogue Annotation for SCN5A residue 1271

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1271
Reference Amino Acid: W - Tryptophan
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1271

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	W1284S	Dravet syndrome	High	9	18930999

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	MFTYVFVLEMLLKWVAYGF----KKYFTNA>W<CWLDFLIVDVSLVSLVAN-T----LGFAEM	1296
SCN1A	VFTYIFILEMLLKWVAYGY----QTYFTNA>W<CWLDFLIVDVSLVSLTAN-A----LGYSEL	1309
SCN2A	VFTYIFILEMLLKWVAYGF----QVYFTNA>W<CWLDFLIVDVSLVSLTAN-A----LGYSEL	1299
SCN3A	VFTYIFILEMLLKWVAYGF----QTYFTNA>W<CWLDFLIVDVSLVSLVAN-A----LGYSEL	1297
SCN4A	VFTYIFIMEMLLKWVAYGF----KVYFTNA>W<CWLDFLIVDVSIISLVAN-W----LGYSEL	1122
SCN7A	IFTYIFILEMLLKWMAYGF----KAYFSNG>W<YRLDFVVVIVFCLSLIGK-T----RE--E-	1022
SCN8A	VFTYIFILEMLLKWTAYGF----VKFFTNA>W<CWLDFLIVAVSLVSLIAN-A----LGYSEL	1289
SCN9A	IFTYIFILEMLLKWIAYGY----KTYFTNA>W<CWLDFLIVDVSLVTLVAN-T----LGYSDL	1272
SCN10A	VFTFIFVFEMLLKWVAYGF----KKYFTNA>W<CWLDFLIVNISLISLTAK-I----LEYSEV	1243
SCN11A	IFTHIFILEMVLKWVAFGF----GKYFTSA>W<CCLDFIIVIVSVTTLI---------N---L	1140
CACNA1A	VFTGVFTFEMVIKMIDLGLVLHQGAYFRDL>W<NILDFIVVSGALVAFAFTGN----SKGKDI	1339
CACNA1B	IFTGVFTFEMVIKMIDLGLLLHPGAYFRDL>W<NILDFIVVSGALVAFAFS-G----SKGKDI	1245
CACNA1C	VFTTIFTIEIALKMTAYGAFLHKGSFCRNY>F<NILDLLVVSVSLISF----G----IQSSAI	991
CACNA1D	AFTAIFTVEILLKMTTFGAFLHKGAFCRNY>F<NLLDMLVVGVSLVSF----G----IQSSAI	997
CACNA1E	VFTGVFTFEMVIKMIDQGLILQDGSYFRDL>W<NILDFVVVVGALVAFALANA-LGTNKGRDI	1251
CACNA1F	AFTSIFTVEILLKMTVFGAFLHRGSFCRSW>F<NMLDLLVVSVSLISF----G----IHSSAI	962
CACNA1G	IFTAVFLAEMTVKVVALGWCFGEQAYLRSS>W<NVLDGLLVLISVIDILVS-MVSD-SGTKIL	1374
CACNA1H	IFTAIFVAEMMVKVVALGLLSGEHAYLQSS>W<NLLDGLLVLVSLVDIVVA-MASA-GGAKIL	1392
CACNA1I	IFTAIFVGEMTLKVVSLGLYFGEQAYLRSS>W<NVLDGFLVFVSIIDIVVS-LASA-GGAKIL	1268
CACNA1S	GFTSVFTVEIVLKMTTYGAFLHKGSFCRNY>F<NMLDLLVVAVSLISM----G----LESSAI	890
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.W1271C	c.3813G>C	Inherited Arrhythmia	BrS	rs199473601	SIFT: deleterious Polyphen: probably damaging
Reports		Inherited Arrhythmia	BrS	An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing. Heart Rhythm. 2010 7(1):33-46. 20129283
Reports		Inherited Arrhythmia	BrS	Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. J Med Genet. 2014 51(1):35-44. doi: 10.1136/jmedgenet-2013-101917. 24136861