TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9977	30154;30155;30156	chr2:178704543;178704542;178704541	chr2:179569270;179569269;179569268
N2AB	9660	29203;29204;29205	chr2:178704543;178704542;178704541	chr2:179569270;179569269;179569268
N2A	8733	26422;26423;26424	chr2:178704543;178704542;178704541	chr2:179569270;179569269;179569268
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-84
• Domain position: 78
• Structural Position: 165
• Q(SASA): 0.5198
• 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
P/S	rs1254687485	None	1.0	None	0.686	0.329	0.206339911435	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1254687485	None	1.0	None	0.686	0.329	0.206339911435	gnomAD-4.0.0	3.84925E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19031E-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
P/A	0.9397	likely_pathogenic	0.8224	pathogenic	-0.448	Destabilizing	0.992	D	0.613	neutral	None	None	None	None	I
P/C	0.9978	likely_pathogenic	0.9926	pathogenic	-0.711	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
P/D	0.9941	likely_pathogenic	0.9806	pathogenic	-0.508	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
P/E	0.9894	likely_pathogenic	0.9631	pathogenic	-0.593	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/F	0.9975	likely_pathogenic	0.9935	pathogenic	-0.628	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
P/G	0.9889	likely_pathogenic	0.9685	pathogenic	-0.578	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
P/H	0.9842	likely_pathogenic	0.9483	pathogenic	-0.059	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
P/I	0.992	likely_pathogenic	0.9767	pathogenic	-0.237	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	I
P/K	0.9901	likely_pathogenic	0.9702	pathogenic	-0.506	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
P/L	0.9656	likely_pathogenic	0.9029	pathogenic	-0.237	Destabilizing	0.467	N	0.505	neutral	None	None	None	None	I
P/M	0.9927	likely_pathogenic	0.9782	pathogenic	-0.537	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/N	0.9912	likely_pathogenic	0.9741	pathogenic	-0.328	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
P/Q	0.9823	likely_pathogenic	0.9413	pathogenic	-0.521	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
P/R	0.9756	likely_pathogenic	0.9262	pathogenic	-0.025	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/S	0.9721	likely_pathogenic	0.9062	pathogenic	-0.64	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
P/T	0.9676	likely_pathogenic	0.8933	pathogenic	-0.625	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
P/V	0.9861	likely_pathogenic	0.9586	pathogenic	-0.276	Destabilizing	0.996	D	0.619	neutral	None	None	None	None	I
P/W	0.9985	likely_pathogenic	0.9955	pathogenic	-0.724	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
P/Y	0.9964	likely_pathogenic	0.9889	pathogenic	-0.431	Destabilizing	1.0	D	0.745	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.