Paralogue Annotation for SCN5A residue 1016

Residue details

Gene: SCN5A
Reference Sequences: LRG: LRG_289, Ensembl variant: ENST00000333535 / ENSP00000328968
Amino Acid Position: 1016
Reference Amino Acid: T - Threonine
Protein Domain: Interdomain Linker II-III

Paralogue Variants mapped to SCN5A residue 1016

Paralogue	Variant	Associated Disease	Mapping Quality	Consensus	Pubmed
SCN8A	G1050S	Cerebral palsy	Low	1	25666757

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	PAALA-A----QGQLPSCIATPYSPPP-PE>T<EKVPPTRKETRFEEG--EQPGQG-------	1037
SCN1A	LDEIK-PLDDLNNKKDSCMSNHT------->-<AEIGKDLDYLKDVNG--TTSGIG-------	1087
SCN2A	LDEIK-PLEDLNNKKDSCISNHT------->T<IEIGKDLNYLKDGNG--TTSGI--------	1078
SCN3A	I-EIH-E----GNKIDSCMSNNT------->G<IEISKELNYLRDGNG--TTSGVG-------	1075
SCN4A	MLSLG-EADGAGEAGEAGETAPE------->D<EKKEPPEEDLKKDNH--ILNHMG-------	898
SCN7A	KDTMD-HVNEVYVKED--ISDHTL------>-<SELSNTQDFLKDKEK--S-S----------	812
SCN8A	ADEVK-PLDELYEKKANCIANHT------->G<ADIHRNGDFQKNGNG--TTSGI--------	1070
SCN9A	SREIR-QAEDLNTKKENYISNHT------->L<AEMSKGHNFLKEKD---KISGF--------	1051
SCN10A	EPELVVKLPLSSSKAENHIAANT------->-<------------ARG--SSGGLQ-------	975
SCN11A	PQQ--------KEVAGGCAAQ--------->S<KDIIPLVMEMKRGSE--TQEELG-------	898
CACNA1A	----Y-NEMDPDERWKAAYTR-HLRPDMKT>H<LDRPLVVDPQENRN-NNTNKSRAAEPTVDQ	848
CACNA1B	----Y-SEMDPEERLRFATTR-HLRPDMKT>H<LDRPLVVELGRDGA-RGPVGGKARPEAAEA	842
CACNA1C	------------------------------>-<------------------------------
CACNA1D	------------------------------>-<------------------------------
CACNA1E	----N-REEAPTMNPLNPLNP-LSSL---->-<--NPLNAHPSLYRR-PRAIEGLAL-----G	839
CACNA1F	------------------------------>-<------------------------------
CACNA1G	----K-SLLPPLIIHTAATPM-SLPKSTST>G<LGEALGPASRRTS-SSGSAEPGA-------	1079
CACNA1H	----G-SLSPPLIMCTAATPM-PTPKS-SP>F<LDAAPSLPDSRRGSSSS-GDP-P-------	1114
CACNA1I	----L-PLGGHLGPAGAAGPA-P--RL-SL>Q<PDPMLVALGSRKSSVMS-LGR-M-------	960
CACNA1S	------------------------------>-<------------------------------
cons	> <

See full Alignment of Paralogues

Known Variants in SCN5A

Protein	CDS	Disease Classification	Disease	dbSNP links	Effect Prediction
p.T1016M	c.3047C>T	Benign		rs199473185	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