TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29912	89959;89960;89961	chr2:178553166;178553165;178553164	chr2:179417893;179417892;179417891
N2AB	28271	85036;85037;85038	chr2:178553166;178553165;178553164	chr2:179417893;179417892;179417891
N2A	27344	82255;82256;82257	chr2:178553166;178553165;178553164	chr2:179417893;179417892;179417891
N2B	20847	62764;62765;62766	chr2:178553166;178553165;178553164	chr2:179417893;179417892;179417891
Novex-1	20972	63139;63140;63141	chr2:178553166;178553165;178553164	chr2:179417893;179417892;179417891
Novex-2	21039	63340;63341;63342	chr2:178553166;178553165;178553164	chr2:179417893;179417892;179417891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-147
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0725
• Predicted PPI site: N

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
L/F	None	None	0.942	N	0.714	0.26	0.389904358541	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
L/P	rs748326514	-1.683	0.99	N	0.874	0.65	0.804452295794	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	1.15996E-04	None	0	0	None	0	None	0	8.88E-06	1.65893E-04
L/P	rs748326514	-1.683	0.99	N	0.874	0.65	0.804452295794	gnomAD-4.0.0	9.58034E-06	None	None	None	None	N	None	0	4.47207E-05	None	0	0	None	0	0	8.09648E-06	0	4.97001E-05

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
L/A	0.9028	likely_pathogenic	0.8553	pathogenic	-2.397	Highly Destabilizing	0.754	D	0.755	deleterious	None	None	None	None	N
L/C	0.7693	likely_pathogenic	0.7439	pathogenic	-1.98	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9991	pathogenic	-2.172	Highly Destabilizing	0.978	D	0.874	deleterious	None	None	None	None	N
L/E	0.9971	likely_pathogenic	0.9932	pathogenic	-1.953	Destabilizing	0.978	D	0.859	deleterious	None	None	None	None	N
L/F	0.5418	ambiguous	0.493	ambiguous	-1.474	Destabilizing	0.942	D	0.714	prob.delet.	N	0.481709634	None	None	N
L/G	0.9871	likely_pathogenic	0.979	pathogenic	-2.93	Highly Destabilizing	0.978	D	0.866	deleterious	None	None	None	None	N
L/H	0.9861	likely_pathogenic	0.975	pathogenic	-2.333	Highly Destabilizing	0.997	D	0.863	deleterious	N	0.505943182	None	None	N
L/I	0.1547	likely_benign	0.1399	benign	-0.864	Destabilizing	0.032	N	0.377	neutral	N	0.458824705	None	None	N
L/K	0.9934	likely_pathogenic	0.9861	pathogenic	-1.612	Destabilizing	0.956	D	0.853	deleterious	None	None	None	None	N
L/M	0.2613	likely_benign	0.2055	benign	-1.046	Destabilizing	0.304	N	0.568	neutral	None	None	None	None	N
L/N	0.9959	likely_pathogenic	0.9916	pathogenic	-1.901	Destabilizing	0.978	D	0.873	deleterious	None	None	None	None	N
L/P	0.9962	likely_pathogenic	0.9931	pathogenic	-1.355	Destabilizing	0.99	D	0.874	deleterious	N	0.505943182	None	None	N
L/Q	0.9772	likely_pathogenic	0.9536	pathogenic	-1.761	Destabilizing	0.978	D	0.867	deleterious	None	None	None	None	N
L/R	0.9839	likely_pathogenic	0.9706	pathogenic	-1.431	Destabilizing	0.942	D	0.857	deleterious	N	0.505943182	None	None	N
L/S	0.9872	likely_pathogenic	0.9756	pathogenic	-2.711	Highly Destabilizing	0.956	D	0.845	deleterious	None	None	None	None	N
L/T	0.9545	likely_pathogenic	0.9214	pathogenic	-2.336	Highly Destabilizing	0.956	D	0.792	deleterious	None	None	None	None	N
L/V	0.1658	likely_benign	0.1382	benign	-1.355	Destabilizing	0.247	N	0.677	prob.neutral	N	0.461902295	None	None	N
L/W	0.9523	likely_pathogenic	0.9291	pathogenic	-1.73	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
L/Y	0.9593	likely_pathogenic	0.9361	pathogenic	-1.452	Destabilizing	0.978	D	0.788	deleterious	None	None	None	None	N

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.