TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1482	4669;4670;4671	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465
N2AB	1482	4669;4670;4671	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465
N2A	1482	4669;4670;4671	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465
N2B	1436	4531;4532;4533	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465
Novex-1	1436	4531;4532;4533	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465
Novex-2	1436	4531;4532;4533	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465
Novex-3	1482	4669;4670;4671	chr2:178777740;178777739;178777738	chr2:179642467;179642466;179642465

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-6
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.2477
• 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
G/S	None	None	0.991	D	0.784	0.652	0.543209242439	gnomAD-4.0.0	3.42052E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49666E-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
G/A	0.9481	likely_pathogenic	0.9443	pathogenic	-0.666	Destabilizing	0.984	D	0.685	prob.neutral	D	0.630034197	None	None	I
G/C	0.9932	likely_pathogenic	0.9931	pathogenic	-0.685	Destabilizing	1.0	D	0.714	prob.delet.	D	0.771233446	None	None	I
G/D	0.9985	likely_pathogenic	0.9982	pathogenic	-1.475	Destabilizing	0.315	N	0.587	neutral	D	0.793295801	None	None	I
G/E	0.9991	likely_pathogenic	0.999	pathogenic	-1.57	Destabilizing	0.993	D	0.818	deleterious	None	None	None	None	I
G/F	0.9993	likely_pathogenic	0.9993	pathogenic	-1.089	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/H	0.9998	likely_pathogenic	0.9998	pathogenic	-1.388	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
G/I	0.9987	likely_pathogenic	0.9986	pathogenic	-0.446	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/K	0.9998	likely_pathogenic	0.9997	pathogenic	-1.511	Destabilizing	0.997	D	0.828	deleterious	None	None	None	None	I
G/L	0.9981	likely_pathogenic	0.9982	pathogenic	-0.446	Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	I
G/M	0.9994	likely_pathogenic	0.9994	pathogenic	-0.289	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
G/N	0.9991	likely_pathogenic	0.999	pathogenic	-1.0	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	I
G/P	0.9996	likely_pathogenic	0.9995	pathogenic	-0.482	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	I
G/Q	0.9994	likely_pathogenic	0.9994	pathogenic	-1.236	Destabilizing	0.997	D	0.8	deleterious	None	None	None	None	I
G/R	0.9991	likely_pathogenic	0.999	pathogenic	-1.08	Destabilizing	0.998	D	0.804	deleterious	D	0.825893571	None	None	I
G/S	0.9675	likely_pathogenic	0.9633	pathogenic	-1.086	Destabilizing	0.991	D	0.784	deleterious	D	0.666609446	None	None	I
G/T	0.9953	likely_pathogenic	0.9953	pathogenic	-1.131	Destabilizing	0.997	D	0.827	deleterious	None	None	None	None	I
G/V	0.9969	likely_pathogenic	0.9967	pathogenic	-0.482	Destabilizing	0.998	D	0.825	deleterious	D	0.756851078	None	None	I
G/W	0.9991	likely_pathogenic	0.9989	pathogenic	-1.443	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
G/Y	0.9995	likely_pathogenic	0.9994	pathogenic	-1.086	Destabilizing	1.0	D	0.786	deleterious	None	None	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.