TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9315	28168;28169;28170	chr2:178711293;178711292;178711291	chr2:179576020;179576019;179576018
N2AB	8998	27217;27218;27219	chr2:178711293;178711292;178711291	chr2:179576020;179576019;179576018
N2A	8071	24436;24437;24438	chr2:178711293;178711292;178711291	chr2:179576020;179576019;179576018
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-79
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2687
• 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/R	None	None	0.999	D	0.815	0.629	0.833005579354	gnomAD-4.0.0	1.59255E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4353E-05	0
G/V	rs1240808727	-0.495	0.999	D	0.795	0.734	0.917018942733	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
G/V	rs1240808727	-0.495	0.999	D	0.795	0.734	0.917018942733	gnomAD-4.0.0	1.59313E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43674E-05	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	0.4067	ambiguous	0.4459	ambiguous	-0.388	Destabilizing	0.992	D	0.635	neutral	D	0.631719565	None	None	I
G/C	0.6314	likely_pathogenic	0.6897	pathogenic	-0.851	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/D	0.3087	likely_benign	0.4284	ambiguous	-0.516	Destabilizing	0.702	D	0.429	neutral	None	None	None	None	I
G/E	0.4201	ambiguous	0.5582	ambiguous	-0.655	Destabilizing	0.998	D	0.8	deleterious	D	0.606858305	None	None	I
G/F	0.83	likely_pathogenic	0.872	pathogenic	-0.937	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/H	0.6674	likely_pathogenic	0.7563	pathogenic	-0.698	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/I	0.7936	likely_pathogenic	0.8684	pathogenic	-0.373	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/K	0.795	likely_pathogenic	0.886	pathogenic	-0.956	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	I
G/L	0.753	likely_pathogenic	0.8005	pathogenic	-0.373	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/M	0.8231	likely_pathogenic	0.8652	pathogenic	-0.39	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/N	0.3735	ambiguous	0.4463	ambiguous	-0.591	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	I
G/P	0.9778	likely_pathogenic	0.9884	pathogenic	-0.341	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/Q	0.6075	likely_pathogenic	0.7127	pathogenic	-0.846	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/R	0.6549	likely_pathogenic	0.7838	pathogenic	-0.531	Destabilizing	0.999	D	0.815	deleterious	D	0.622634783	None	None	I
G/S	0.1763	likely_benign	0.1991	benign	-0.797	Destabilizing	0.967	D	0.419	neutral	None	None	None	None	I
G/T	0.4703	ambiguous	0.5589	ambiguous	-0.86	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	I
G/V	0.7	likely_pathogenic	0.8017	pathogenic	-0.341	Destabilizing	0.999	D	0.795	deleterious	D	0.638855949	None	None	I
G/W	0.7203	likely_pathogenic	0.8194	pathogenic	-1.142	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/Y	0.7084	likely_pathogenic	0.7911	pathogenic	-0.78	Destabilizing	1.0	D	0.817	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.