TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22638	68137;68138;68139	chr2:178579118;178579117;178579116	chr2:179443845;179443844;179443843
N2AB	20997	63214;63215;63216	chr2:178579118;178579117;178579116	chr2:179443845;179443844;179443843
N2A	20070	60433;60434;60435	chr2:178579118;178579117;178579116	chr2:179443845;179443844;179443843
N2B	13573	40942;40943;40944	chr2:178579118;178579117;178579116	chr2:179443845;179443844;179443843
Novex-1	13698	41317;41318;41319	chr2:178579118;178579117;178579116	chr2:179443845;179443844;179443843
Novex-2	13765	41518;41519;41520	chr2:178579118;178579117;178579116	chr2:179443845;179443844;179443843
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-127
• Domain position: 79
• Structural Position: 174
• Q(SASA): 0.1228
• 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
I/K	rs2047107763	None	0.966	N	0.755	0.482	0.801924819766	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
I/V	rs1300737822	None	0.005	N	0.244	0.072	0.336647302497	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1300737822	None	0.005	N	0.244	0.072	0.336647302497	gnomAD-4.0.0	6.5754E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47119E-05	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
I/A	0.9298	likely_pathogenic	0.9331	pathogenic	-2.296	Highly Destabilizing	0.525	D	0.578	neutral	None	None	None	None	I
I/C	0.9102	likely_pathogenic	0.9196	pathogenic	-1.599	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
I/D	0.9986	likely_pathogenic	0.9986	pathogenic	-2.062	Highly Destabilizing	0.991	D	0.769	deleterious	None	None	None	None	I
I/E	0.9948	likely_pathogenic	0.995	pathogenic	-1.831	Destabilizing	0.974	D	0.754	deleterious	None	None	None	None	I
I/F	0.4157	ambiguous	0.4279	ambiguous	-1.338	Destabilizing	0.949	D	0.607	neutral	None	None	None	None	I
I/G	0.9896	likely_pathogenic	0.9901	pathogenic	-2.854	Highly Destabilizing	0.974	D	0.755	deleterious	None	None	None	None	I
I/H	0.9913	likely_pathogenic	0.9919	pathogenic	-2.191	Highly Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	I
I/K	0.9898	likely_pathogenic	0.9898	pathogenic	-1.599	Destabilizing	0.966	D	0.755	deleterious	N	0.478559763	None	None	I
I/L	0.1877	likely_benign	0.1928	benign	-0.697	Destabilizing	0.002	N	0.275	neutral	N	0.398103454	None	None	I
I/M	0.2212	likely_benign	0.2245	benign	-0.678	Destabilizing	0.934	D	0.615	neutral	N	0.477799295	None	None	I
I/N	0.9835	likely_pathogenic	0.9827	pathogenic	-1.907	Destabilizing	0.991	D	0.78	deleterious	None	None	None	None	I
I/P	0.9931	likely_pathogenic	0.9934	pathogenic	-1.209	Destabilizing	0.991	D	0.776	deleterious	None	None	None	None	I
I/Q	0.9885	likely_pathogenic	0.9886	pathogenic	-1.741	Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	I
I/R	0.983	likely_pathogenic	0.9835	pathogenic	-1.409	Destabilizing	0.966	D	0.779	deleterious	N	0.478559763	None	None	I
I/S	0.973	likely_pathogenic	0.9738	pathogenic	-2.702	Highly Destabilizing	0.974	D	0.721	prob.delet.	None	None	None	None	I
I/T	0.9395	likely_pathogenic	0.9396	pathogenic	-2.306	Highly Destabilizing	0.801	D	0.627	neutral	N	0.478559763	None	None	I
I/V	0.0748	likely_benign	0.0778	benign	-1.209	Destabilizing	0.005	N	0.244	neutral	N	0.405179434	None	None	I
I/W	0.9779	likely_pathogenic	0.9808	pathogenic	-1.625	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	I
I/Y	0.9388	likely_pathogenic	0.9457	pathogenic	-1.322	Destabilizing	0.974	D	0.699	prob.neutral	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.