TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27656	83191;83192;83193	chr2:178563166;178563165;178563164	chr2:179427893;179427892;179427891
N2AB	26015	78268;78269;78270	chr2:178563166;178563165;178563164	chr2:179427893;179427892;179427891
N2A	25088	75487;75488;75489	chr2:178563166;178563165;178563164	chr2:179427893;179427892;179427891
N2B	18591	55996;55997;55998	chr2:178563166;178563165;178563164	chr2:179427893;179427892;179427891
Novex-1	18716	56371;56372;56373	chr2:178563166;178563165;178563164	chr2:179427893;179427892;179427891
Novex-2	18783	56572;56573;56574	chr2:178563166;178563165;178563164	chr2:179427893;179427892;179427891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-89
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.786
• 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
E/G	None	None	0.988	N	0.647	0.507	0.449669948863	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85869E-06	0	0
E/K	rs1001344341	None	0.067	N	0.342	0.211	None	gnomAD-4.0.0	2.05272E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69853E-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
E/A	0.339	likely_benign	0.3179	benign	-0.438	Destabilizing	0.919	D	0.605	neutral	N	0.478116734	None	None	I
E/C	0.9366	likely_pathogenic	0.9259	pathogenic	-0.137	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/D	0.1694	likely_benign	0.1902	benign	-0.428	Destabilizing	0.958	D	0.525	neutral	N	0.509419388	None	None	I
E/F	0.8841	likely_pathogenic	0.8658	pathogenic	-0.353	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/G	0.4164	ambiguous	0.3911	ambiguous	-0.638	Destabilizing	0.988	D	0.647	neutral	N	0.489459813	None	None	I
E/H	0.7642	likely_pathogenic	0.724	pathogenic	-0.116	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
E/I	0.544	ambiguous	0.502	ambiguous	0.059	Stabilizing	0.995	D	0.73	prob.delet.	None	None	None	None	I
E/K	0.3136	likely_benign	0.2775	benign	0.076	Stabilizing	0.067	N	0.342	neutral	N	0.513747773	None	None	I
E/L	0.577	likely_pathogenic	0.5365	ambiguous	0.059	Stabilizing	0.991	D	0.702	prob.neutral	None	None	None	None	I
E/M	0.626	likely_pathogenic	0.5945	pathogenic	0.141	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/N	0.46	ambiguous	0.4662	ambiguous	-0.121	Destabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	I
E/P	0.6208	likely_pathogenic	0.5991	pathogenic	-0.087	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
E/Q	0.2632	likely_benign	0.232	benign	-0.101	Destabilizing	0.958	D	0.656	neutral	N	0.477382719	None	None	I
E/R	0.5275	ambiguous	0.4733	ambiguous	0.344	Stabilizing	0.982	D	0.695	prob.neutral	None	None	None	None	I
E/S	0.3961	ambiguous	0.3882	ambiguous	-0.32	Destabilizing	0.968	D	0.618	neutral	None	None	None	None	I
E/T	0.4665	ambiguous	0.4569	ambiguous	-0.168	Destabilizing	0.991	D	0.674	neutral	None	None	None	None	I
E/V	0.3714	ambiguous	0.3392	benign	-0.087	Destabilizing	0.988	D	0.709	prob.delet.	N	0.4855627	None	None	I
E/W	0.9718	likely_pathogenic	0.9656	pathogenic	-0.22	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
E/Y	0.8065	likely_pathogenic	0.7865	pathogenic	-0.124	Destabilizing	0.998	D	0.73	prob.delet.	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.