Paralogue Annotation for SCN5A residue 335

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 335
Reference Amino Acid: C - Cysteine
Protein Domain: TM Domain 1

Paralogue Variants mapped to SCN5A residue 335

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN1A	C345R	Dravet syndrome	High	5	18930999
SCN1A	C345X	Dravet syndrome C	High	5	21248271, 25525159
SCN1A	C345W	Dravet syndrome C ?	High	5	21248271
SCN1A	C345Y	Myoclonic epilepsy of infancy	High	5	22140375

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	LSD-PENYLLKNGTSDVLLCGNSSDAG-T->C<-PEGYRCLKAGENPDHGYTSFDSFAWAFLA	364
SCN1A	IQD-SRYHYFLEGFLDALLCGNSSDAG-Q->C<-PEGYMCVKAGRNPNYGYTSFDTFSWAFLS	374
SCN2A	IED-KSHFYFLEGQNDALLCGNSSDAG-Q->C<-PEGYICVKAGRNPNYGYTSFDTFSWAFLS	376
SCN3A	IGD-DSHFYVLDGQKDPLLCGNGSDAG-Q->C<-PEGYICVKAGRNPNYGYTSFDTFSWAFLS	375
SCN4A	ISD-EGNFYFLEGSNDALLCGNSSDAG-H->C<-PEGYECIKTGRNPNYGYTSYDTFSWAFLA	398
SCN7A	IRE-TENFYYLEGERYALLCGNRTDAG-Q->C<-PEGYVCVKAGINPDQGFTNFDSFGWALFA	345
SCN8A	INN-KTNFYTVPGMLEPLLCGNSSDAG-Q->C<-PEGYQCMKAGRNPNYGYTSFDTFSWAFLA	362
SCN9A	----RKYFYYLEGSKDALLCGFSTDSG-Q->C<-PEGYTCVKIGRNPDYGYTSFDTFSWAFLA	353
SCN10A	HRK-PDIYINKRGTSDPLLCGNGSDSG-H->C<-PDGYICLKTSDNPDFNYTSFDSFAWAFLS	348
SCN11A	-AY-DHCFEKKENSPEFKMCGIWMGNS-A->C<-SIQYECKHTKINPDYNYTNFDNFGWSFLA	351
CACNA1A	------------E--SPAPCGTEEPA-RT->C<-PNGTKCQPYWEGPNNGITQFDNILFAVLT	310
CACNA1B	------------V--GDFPCGKEAPA-RL->C<-EGDTECREYWPGPNFGITNFDNILFAILT	306
CACNA1C	------------D--DPSPCALETGHGRQ->C<QN-GTVCKPGWDGPKHGITNFDNFAFAMLT	355
CACNA1D	------------E--DPAPCAFSGNGR-Q->C<TANGTECRSGWVGPNGGITNFDNFAFAMLT	356
CACNA1E	------------D--PPHPCGVQG------>C<-PAGYEC-KDWIGPNDGITQFDNILFAVLT	301
CACNA1F	------------E--DPSPCASSGSGR-A->C<TLNQTECRGRWPGPNGGITNFDNFFFAMLT	322
CACNA1G	PCG-LDYEAYNS---------SSNTTC-VN>W<NQYYTNCSAGEHNPFKGAINFDNIGYAWIA	346
CACNA1H	PCT-LGWEAYTQP--QAEGVGAARNAC-IN>W<NQYYNVCRSGDSNPHNGAINFDNIGYAWIA	370
CACNA1I	ECCLSKDDVYDFG--AGRQDLNASGLC-VN>W<NRYYNVCRTGSANPHKGAINFDNIGYAWIV	349
CACNA1S	------------E--EPSPCARTGSGR-R->C<TINGSECRGGWPGPNHGITHFDNFGFSMLT	284
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.C335S	c.1003T>A	Inherited Arrhythmia	BrS		SIFT: Polyphen:
Reports		Inherited Arrhythmia	BrS	Testing the burden of rare variation in arrhythmia-susceptibility genes provides new insights into molecular diagnosis for Brugada syndrome. Hum Mol Genet. 2015 24(10):2757-63. doi: 10.1093/hmg/ddv036. 25650408