TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17366	52321;52322;52323	chr2:178609214;178609213;178609212	chr2:179473941;179473940;179473939
N2AB	15725	47398;47399;47400	chr2:178609214;178609213;178609212	chr2:179473941;179473940;179473939
N2A	14798	44617;44618;44619	chr2:178609214;178609213;178609212	chr2:179473941;179473940;179473939
N2B	8301	25126;25127;25128	chr2:178609214;178609213;178609212	chr2:179473941;179473940;179473939
Novex-1	8426	25501;25502;25503	chr2:178609214;178609213;178609212	chr2:179473941;179473940;179473939
Novex-2	8493	25702;25703;25704	chr2:178609214;178609213;178609212	chr2:179473941;179473940;179473939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-112
• Domain position: 116
• Structural Position: 177
• Q(SASA): 0.2123
• 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
V/A	None	None	0.977	D	0.706	0.759	0.784753558091	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/M	None	None	0.993	D	0.831	0.608	0.7613135738	gnomAD-4.0.0	1.47234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.58128E-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
V/A	0.9716	likely_pathogenic	0.9716	pathogenic	-2.126	Highly Destabilizing	0.977	D	0.706	prob.neutral	D	0.595534035	None	None	N
V/C	0.9884	likely_pathogenic	0.9889	pathogenic	-1.852	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9988	pathogenic	-3.004	Highly Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
V/E	0.9971	likely_pathogenic	0.9967	pathogenic	-2.904	Highly Destabilizing	0.999	D	0.801	deleterious	D	0.596139448	None	None	N
V/F	0.9597	likely_pathogenic	0.9573	pathogenic	-1.382	Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
V/G	0.9872	likely_pathogenic	0.9859	pathogenic	-2.513	Highly Destabilizing	0.999	D	0.791	deleterious	D	0.596139448	None	None	N
V/H	0.999	likely_pathogenic	0.9989	pathogenic	-1.96	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/I	0.1123	likely_benign	0.1174	benign	-1.089	Destabilizing	0.15	N	0.581	neutral	None	None	None	None	N
V/K	0.9978	likely_pathogenic	0.9976	pathogenic	-1.764	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
V/L	0.9076	likely_pathogenic	0.9051	pathogenic	-1.089	Destabilizing	0.898	D	0.707	prob.neutral	D	0.593515992	None	None	N
V/M	0.917	likely_pathogenic	0.9127	pathogenic	-1.155	Destabilizing	0.993	D	0.831	deleterious	D	0.595735839	None	None	N
V/N	0.9937	likely_pathogenic	0.9929	pathogenic	-1.912	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
V/P	0.9928	likely_pathogenic	0.9937	pathogenic	-1.409	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
V/Q	0.997	likely_pathogenic	0.9968	pathogenic	-1.991	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/R	0.9954	likely_pathogenic	0.9952	pathogenic	-1.309	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/S	0.9847	likely_pathogenic	0.983	pathogenic	-2.397	Highly Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
V/T	0.9387	likely_pathogenic	0.9329	pathogenic	-2.193	Highly Destabilizing	0.983	D	0.777	deleterious	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.72	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/Y	0.9973	likely_pathogenic	0.9972	pathogenic	-1.455	Destabilizing	0.999	D	0.792	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.