Paralogue Annotation for SCN5A residue 1419

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1419
Reference Amino Acid: K - Lysine
Protein Domain: TM Domain 3

Paralogue Variants mapped to SCN5A residue 1419

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CACNA1C	E1115K	Brugada syndrome (shorter-than-normal QT interval)	Medium	9	20817017
SCN2A	K1422E	Spasms, infantile, and bitemporal glucose hypometa	High	9	23827426, 25262651
SCN1A	K1432R	Dravet syndrome	High	9	25459968

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	GE--LYWTKVKVNFDNVGAGYLALLQVATF>K<GWMDIMYAAVDSRGYEEQPQWEYNLYMYIY	1449
SCN1A	NET-ARWKNVKVNFDNVGFGYLSLLQVATF>K<GWMDIMYAAVDSRNVELQPKYEESLYMYLY	1462
SCN2A	NQT-ARWKNVKVNFDNVGLGYLSLLQVATF>K<GWMDIMYAAVDSRNVELQPKYEDNLYMYLY	1452
SCN3A	-Q--ARWKNVKVNFDNVGAGYLALLQVATF>K<GWMDIMYAAVDSRDVKLQPVYEENLYMYLY	1447
SCN4A	GQ--VRWLNVKVNYDNVGLGYLSLLQVATF>K<GWMDIMYAAVDSREKEEQPQYEVNLYMYLY	1274
SCN7A	ES--MLWENAKMNFDNVGNGFLSLLQVATF>N<GWITIMNSAIDSVAVNIQPHFEVNIYMYCY	1172
SCN8A	NNTEIRWKNVKINFDNVGAGYLALLQVATF>K<GWMDIMYAAVDSRKPDEQPKYEDNIYMYIY	1443
SCN9A	SQN-VRWKNLKVNFDNVGLGYLSLLQVATF>K<GWTIIMYAAVDSVNVDKQPKYEYSLYMYIY	1425
SCN10A	GS--FFWVNVKVNFDNVAMGYLALLQVATF>K<GWMDIMYAAVDSREVNMQPKWEDNVYMYLY	1397
SCN11A	----FSWINQKVNFDNVGNAYLALLQVATF>K<GWMDIIYAAVDSTEKEQQPEFESNSLGYIY	1287
CACNA1A	R--DREWKKYEFHYDNVLWALLTLFTVSTG>E<GWPQVLKHSVDATFENQGPSPGYRMEMSIF	1490
CACNA1B	Q--PRQWKKYDFHYDNVLWALLTLFTVSTG>E<GWPMVLKHSVDATYEEQGPSPGYRMELSIF	1396
CACNA1C	Q--PRSWENSKFDFDNVLAAMMALFTVSTF>E<GWPELLYRSIDSHTEDKGPIYNYRVEISIF	1145
CACNA1D	R--ERIWQNSDFNFDNVLSAMMALFTVSTF>E<GWPALLYKAIDSNGENIGPIYNHRVEISIF	1151
CACNA1E	K--GREWKRHEFHYDNIIWALLTLFTVSTG>E<GWPQVLQHSVDVTEEDRGPSRSNRMEMSIF	1402
CACNA1F	R--ERLWVNSDFNFDNVLSAMMALFTVSTF>E<GWPALLYKAIDAYAEDHGPIYNYRVEISVF	1116
CACNA1G	A--SYRWVRHKYNFDNLGQALMSLFVLASK>D<GWVDIMYDGLDAVGVDQQPIMNHNPWMLLY	1516
CACNA1H	A--HYRWVRRKYNFDNLGQALMSLFVLSSK>D<GWVNIMYDGLDAVGVDQQPVQNHNPWMLLY	1534
CACNA1I	A--NYRWVHHKYNFDNLGQALMSLFVLASK>D<GWVNIMYNGLDAVAVDQQPVTNHNPWMLLY	1410
CACNA1S	R--HREWVHSDFHFDNVLSAMMSLFTVSTF>E<GWPQLLYKAIDSNAEDVGPIYNNRVEMAIF	1044
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.K1419E	c.4255A>G	Inherited Arrhythmia	BrS	rs199473242	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