Paralogue Annotation for SCN5A residue 672

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 672
Reference Amino Acid: A - Alanine
Protein Domain: Interdomain Linker I-II

Paralogue Variants mapped to SCN5A residue 672

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN10A	V620I	Brugada syndrome	Low	3	24998131

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	SQAPCVD-GFEEPGARQR-A-LSAVSVLTS>A<----L-EELE-ESR----------------	680
SCN1A	SFHVSMD-FLEDPSQRQR-A-MSIASILTN>T<----V-EELE-ESR----------------	731
SCN2A	SYHVSMD-LLEDPTSRQR-A-MSIASILTN>T<----M-EELE-ESR----------------	722
SCN3A	SYQISME-MLEDSSGRQR-A-VSIASILTN>T<----M-EELE-ESR----------------	723
SCN4A	--------E---KGAPRQ-S-SSGDSGISD>A<----M-EELE-EAH----------------	541
SCN7A	STDTSLD-VLEDATLRHK------------>-<------EELE-KSK----------------	468
SCN8A	SLLVSMD-QLASYGRKDR-I-NSIMSVVTN>T<L---V-EELE-ESQ----------------	716
SCN9A	SYLLSED-MLNDPNLRQR-A-MSRASILTN>T<----V-EELE-ESR----------------	696
SCN10A	KTFLSAE-YLDEPFRAQR-A-MSVVSIITS>V<----L-EELE-ESE----------------	628
SCN11A	LSLDHFD-EHGDPLQRQR-A-LSAVSILTI>T<----M-KEQE-KSQ----------------	540
CACNA1A	NPEEAED-QLA----DIA-S-VG------->-<------------------------------	450
CACNA1B	HAEEGED-RFA----DLC-A-VG------->-<------------------------------	446
CACNA1C	NTENVAG-G-D----IEGEN-CG------->-<------------------------------	490
CACNA1D	NTENVSG-EGE----NRG-C-CGSLWCWWR>-<------RRGA-AKA----------------	504
CACNA1E	TRDSSDE-HCV----DIS-S-VG------->-<------------------------------	439
CACNA1F	-THSTSSHASL----P-A-SDTGSMTETQG>-<------DEDE-EEG----------------	490
CACNA1G	SGACGPD-SCP----YCA-R-AG-----AG>-<----EVELADREMP-DSDSEAVYEFTQDAQ	701
CACNA1H	TLTCELK-SCP----YCT-R-AL-----ED>-<P---EGELSGSESG-DSDGRGVYEFTQDVR	735
CACNA1I	----DPA-SCP----CCQ-H-ED-----GR>-<RPSGLGS---TDSGQEGSGSGSSAGGEDE-	588
CACNA1S	Y-EI-------------------------->-<------------AG----------------	403
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.A672T	c.2014G>A	Putative Benign		rs199473140	SIFT: tolerated Polyphen: benign
Reports		Putative Benign		Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants. Circulation. 2009 120(18):1752-60. 19841300
		Putative Benign		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
		Unknown		Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. Heart. 2015 101(4):294-301. doi: 10.1136/heartjnl-2014-306387. 25351510