TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13814	41665;41666;41667	chr2:178636131;178636130;178636129	chr2:179500858;179500857;179500856
N2AB	12173	36742;36743;36744	chr2:178636131;178636130;178636129	chr2:179500858;179500857;179500856
N2A	11246	33961;33962;33963	chr2:178636131;178636130;178636129	chr2:179500858;179500857;179500856
N2B	4749	14470;14471;14472	chr2:178636131;178636130;178636129	chr2:179500858;179500857;179500856
Novex-1	4874	14845;14846;14847	chr2:178636131;178636130;178636129	chr2:179500858;179500857;179500856
Novex-2	4941	15046;15047;15048	chr2:178636131;178636130;178636129	chr2:179500858;179500857;179500856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-88
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.2596
• 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
K/R	None	None	0.235	N	0.25	0.15	0.146414634003	gnomAD-4.0.0	6.84457E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09699E-06	0	1.65739E-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
K/A	0.9927	likely_pathogenic	0.9916	pathogenic	-0.912	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	N
K/C	0.983	likely_pathogenic	0.9829	pathogenic	-0.945	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/D	0.9986	likely_pathogenic	0.9984	pathogenic	-0.244	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
K/E	0.9824	likely_pathogenic	0.9807	pathogenic	-0.126	Destabilizing	0.977	D	0.533	neutral	N	0.495009172	None	None	N
K/F	0.9953	likely_pathogenic	0.9953	pathogenic	-0.813	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
K/G	0.9962	likely_pathogenic	0.9952	pathogenic	-1.264	Destabilizing	0.998	D	0.686	prob.delet.	None	None	None	None	N
K/H	0.8441	likely_pathogenic	0.8493	pathogenic	-1.699	Destabilizing	0.999	D	0.723	deleterious	None	None	None	None	N
K/I	0.9719	likely_pathogenic	0.9762	pathogenic	0.004	Stabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
K/L	0.9702	likely_pathogenic	0.9687	pathogenic	0.004	Stabilizing	0.995	D	0.686	prob.delet.	None	None	None	None	N
K/M	0.9421	likely_pathogenic	0.943	pathogenic	0.027	Stabilizing	1.0	D	0.73	deleterious	N	0.459405211	None	None	N
K/N	0.9921	likely_pathogenic	0.9911	pathogenic	-0.62	Destabilizing	0.993	D	0.674	prob.neutral	N	0.495009172	None	None	N
K/P	0.9995	likely_pathogenic	0.9993	pathogenic	-0.273	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/Q	0.8797	likely_pathogenic	0.8682	pathogenic	-0.733	Destabilizing	0.993	D	0.663	prob.neutral	N	0.42210314	None	None	N
K/R	0.2057	likely_benign	0.2007	benign	-0.647	Destabilizing	0.235	N	0.25	neutral	N	0.351319367	None	None	N
K/S	0.9964	likely_pathogenic	0.9957	pathogenic	-1.377	Destabilizing	0.983	D	0.592	neutral	None	None	None	None	N
K/T	0.9893	likely_pathogenic	0.988	pathogenic	-1.043	Destabilizing	0.997	D	0.691	prob.delet.	N	0.436816807	None	None	N
K/V	0.9607	likely_pathogenic	0.9664	pathogenic	-0.273	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
K/W	0.9911	likely_pathogenic	0.991	pathogenic	-0.645	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/Y	0.976	likely_pathogenic	0.9751	pathogenic	-0.311	Destabilizing	0.999	D	0.786	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.