Paralogue Annotation for SCN5A residue 232

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 232
Reference Amino Acid: V - Valine
Protein Domain: TM Domain 1

Paralogue Variants mapped to SCN5A residue 232

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
CACNA1H	R212R	Autism spectrum disorder ?	Medium	9	16754686

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	------------NLSALRTFRVLRALKTIS>V<IPGLKTIVGALIQSVKKLADVMVLTVFCLS	262
SCN1A	------------NVSALRTFRVLRALKTIS>V<IPGLKTIVGALIQSVKKLSDVMILTVFCLS	259
SCN2A	------------NVSALRTFRVLRALKTIS>V<IPGLKTIVGALIQSVKKLSDVMILTVFCLS	260
SCN3A	------------NVSALRTFRVLRALKTIS>V<IPGLKTIVGALIQSVKKLSDVMILTVFCLS	259
SCN4A	------------NISALRTFRVLRALKTIT>V<IPGLKTIVGALIQSVKKLSDVMILTVFCLS	262
SCN7A	------------FIPTLQTARTLRILKIIP>L<NQGLKSLVGVLIHCLKQLIGVIILTLFFLS	249
SCN8A	------------NVSALRTFRVLRALKTIS>V<IPGLKTIVGALIQSVKKLSDVMILTVFCLS	263
SCN9A	------------NVSALRTFRVLRALKTIS>V<IPGLKTIVGALIQSVKKLSDVMILTVFCLS	257
SCN10A	------------GISGLRTFRVLRALKTVS>V<IPGLKVIVGALIHSVKKLADVTILTIFCLS	258
SCN11A	-----------IKLLPLRTFRVFRALKAIS>V<VSRLKVIVGALLRSVKKLVNVIILTFFCLS	265
CACNA1A	------------DLRTLRAVRVLRPLKLVS>G<IPSLQVVLKSIMKAMIPLLQIGLLLFFAIL	238
CACNA1B	------------DLRTLRAVRVLRPLKLVS>G<IPSLQVVLKSIMKAMVPLLQIGLLLFFAIL	235
CACNA1C	GANALGGKGAGFDVKALRAFRVLRPLRLVS>G<VPSLQVVLNSIIKAMVPLLHIALLVLFVII	280
CACNA1D	GGNHSSGKSGGFDVKALRAFRVLRPLRLVS>G<VPSLQVVLNSIIKAMVPLLHIALLVLFVII	283
CACNA1E	---------THVDLRTLRAVRVLRPLKLVS>G<IPSLQIVLKSIMKAMVPLLQIGLLLFFAIL	233
CACNA1F	DAPHTGGKPGGFDVKALRAFRVLRPLRLVS>G<VPSLHIVLNSIMKALVPLLHIALLVLFVII	249
CACNA1G	----------NVSFSAVRTVRVLRPLRAIN>R<VPSMRILVTLLLDTLPMLGNVLLLCFFVFF	223
CACNA1H	----------NVSLSAIRTVRVLRPLRAIN>R<VPSMRILVTLLLDTLPMLGNVLLLCFFVFF	242
CACNA1I	----------NINLSAIRTVRVLRPLKAIN>R<VPSMRILVNLLLDTLPMLGNVLLLCFFVFF	221
CACNA1S	HTAPMSSKGAGLDVKALRAFRVLRPLRLVS>G<VPSLQVVLNSIFKAMLPLFHIALLVLFMVI	208
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.V232I	c.694G>A	Inherited Arrhythmia	BrS	rs45471994	SIFT: tolerated Polyphen: possibly damaging
Reports		Other Cardiac Phenotype		Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel. Circ Res. 2008 103(4):396-404. 18599870
		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
		Other Cardiac Phenotype		High prevalence of genetic variants previously associated with Brugada syndrome in new exome data. Clin Genet. 2013 23414114
		Other Cardiac Phenotype		Actionable, pathogenic incidental findings in 1,000 participants' exomes. Am J Hum Genet. 2013 93(4):631-40. doi: 10.1016/j.ajhg.2013.08.006. 24055113
		Other Cardiac Phenotype		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
		Unknown		Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015 25(3):305-15. doi: 10.1101/gr.183483.114. 25637381