TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1534	4825;4826;4827	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190
N2AB	1534	4825;4826;4827	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190
N2A	1534	4825;4826;4827	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190
N2B	1488	4687;4688;4689	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190
Novex-1	1488	4687;4688;4689	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190
Novex-2	1488	4687;4688;4689	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190
Novex-3	1534	4825;4826;4827	chr2:178777465;178777464;178777463	chr2:179642192;179642191;179642190

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-6
• Domain position: 78
• Structural Position: 161
• Q(SASA): 0.1634
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
N/K	None	None	1.0	D	0.728	0.508	0.395441342475	gnomAD-4.0.0	3.42088E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49677E-06	0	0
N/T	None	None	0.999	D	0.703	0.869	0.774764864444	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
N/A	0.9978	likely_pathogenic	0.9982	pathogenic	-0.538	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
N/C	0.9838	likely_pathogenic	0.9841	pathogenic	-0.083	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
N/D	0.9914	likely_pathogenic	0.9932	pathogenic	-1.609	Destabilizing	0.999	D	0.622	neutral	D	0.824473024	None	None	I
N/E	0.9987	likely_pathogenic	0.9988	pathogenic	-1.508	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
N/F	0.9997	likely_pathogenic	0.9997	pathogenic	-0.441	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
N/G	0.9898	likely_pathogenic	0.991	pathogenic	-0.857	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	I
N/H	0.9885	likely_pathogenic	0.9902	pathogenic	-0.747	Destabilizing	1.0	D	0.741	deleterious	D	0.822904555	None	None	I
N/I	0.9978	likely_pathogenic	0.9979	pathogenic	0.261	Stabilizing	1.0	D	0.705	prob.neutral	D	0.789877398	None	None	I
N/K	0.9991	likely_pathogenic	0.9993	pathogenic	-0.286	Destabilizing	1.0	D	0.728	prob.delet.	D	0.823466487	None	None	I
N/L	0.994	likely_pathogenic	0.994	pathogenic	0.261	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
N/M	0.9963	likely_pathogenic	0.9966	pathogenic	0.732	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/P	0.9993	likely_pathogenic	0.9994	pathogenic	0.024	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/Q	0.9987	likely_pathogenic	0.9989	pathogenic	-1.106	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/R	0.9991	likely_pathogenic	0.9992	pathogenic	-0.246	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
N/S	0.9165	likely_pathogenic	0.9278	pathogenic	-0.891	Destabilizing	0.999	D	0.586	neutral	D	0.582273225	None	None	I
N/T	0.978	likely_pathogenic	0.9809	pathogenic	-0.633	Destabilizing	0.999	D	0.703	prob.neutral	D	0.755356806	None	None	I
N/V	0.9972	likely_pathogenic	0.9974	pathogenic	0.024	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
N/W	0.9999	likely_pathogenic	0.9999	pathogenic	-0.345	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
N/Y	0.9964	likely_pathogenic	0.9964	pathogenic	-0.016	Destabilizing	1.0	D	0.722	prob.delet.	D	0.822966967	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.