TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16814	50665;50666;50667	chr2:178611869;178611868;178611867	chr2:179476596;179476595;179476594
N2AB	15173	45742;45743;45744	chr2:178611869;178611868;178611867	chr2:179476596;179476595;179476594
N2A	14246	42961;42962;42963	chr2:178611869;178611868;178611867	chr2:179476596;179476595;179476594
N2B	7749	23470;23471;23472	chr2:178611869;178611868;178611867	chr2:179476596;179476595;179476594
Novex-1	7874	23845;23846;23847	chr2:178611869;178611868;178611867	chr2:179476596;179476595;179476594
Novex-2	7941	24046;24047;24048	chr2:178611869;178611868;178611867	chr2:179476596;179476595;179476594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-10
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.2997
• 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
T/I	None	None	1.0	D	0.798	0.473	0.55999961142	gnomAD-4.0.0	6.84561E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9981E-07	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
T/A	0.2147	likely_benign	0.215	benign	-0.463	Destabilizing	0.999	D	0.53	neutral	N	0.519595938	None	None	N
T/C	0.8052	likely_pathogenic	0.7325	pathogenic	-0.396	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/D	0.7359	likely_pathogenic	0.7672	pathogenic	0.093	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/E	0.651	likely_pathogenic	0.6883	pathogenic	0.054	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/F	0.6702	likely_pathogenic	0.6614	pathogenic	-0.721	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/G	0.4861	ambiguous	0.4891	ambiguous	-0.657	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/H	0.627	likely_pathogenic	0.5956	pathogenic	-0.856	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
T/I	0.5166	ambiguous	0.528	ambiguous	-0.059	Destabilizing	1.0	D	0.798	deleterious	D	0.522576938	None	None	N
T/K	0.4825	ambiguous	0.4981	ambiguous	-0.566	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/L	0.246	likely_benign	0.236	benign	-0.059	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
T/M	0.1852	likely_benign	0.1772	benign	-0.022	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/N	0.293	likely_benign	0.3048	benign	-0.406	Destabilizing	1.0	D	0.687	prob.neutral	N	0.504549327	None	None	N
T/P	0.3054	likely_benign	0.3112	benign	-0.163	Destabilizing	1.0	D	0.806	deleterious	N	0.473673009	None	None	N
T/Q	0.4846	ambiguous	0.4938	ambiguous	-0.568	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
T/R	0.4422	ambiguous	0.4532	ambiguous	-0.283	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
T/S	0.236	likely_benign	0.2339	benign	-0.639	Destabilizing	0.999	D	0.495	neutral	N	0.481788515	None	None	N
T/V	0.3678	ambiguous	0.3614	ambiguous	-0.163	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
T/W	0.8779	likely_pathogenic	0.8698	pathogenic	-0.721	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/Y	0.7308	likely_pathogenic	0.7281	pathogenic	-0.461	Destabilizing	1.0	D	0.828	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.