TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16847	50764;50765;50766	chr2:178611770;178611769;178611768	chr2:179476497;179476496;179476495
N2AB	15206	45841;45842;45843	chr2:178611770;178611769;178611768	chr2:179476497;179476496;179476495
N2A	14279	43060;43061;43062	chr2:178611770;178611769;178611768	chr2:179476497;179476496;179476495
N2B	7782	23569;23570;23571	chr2:178611770;178611769;178611768	chr2:179476497;179476496;179476495
Novex-1	7907	23944;23945;23946	chr2:178611770;178611769;178611768	chr2:179476497;179476496;179476495
Novex-2	7974	24145;24146;24147	chr2:178611770;178611769;178611768	chr2:179476497;179476496;179476495
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: Fn3-10
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.6015
• 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
E/G	rs760623859	-1.08	0.003	N	0.392	0.202	0.254761474806	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.61E-05	None	0	0	0
E/G	rs760623859	-1.08	0.003	N	0.392	0.202	0.254761474806	gnomAD-4.0.0	4.78643E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.8796E-05	3.03177E-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
E/A	0.2667	likely_benign	0.2463	benign	-0.843	Destabilizing	0.297	N	0.499	neutral	N	0.475197978	None	None	N
E/C	0.929	likely_pathogenic	0.8943	pathogenic	-0.248	Destabilizing	0.989	D	0.779	deleterious	None	None	None	None	N
E/D	0.3112	likely_benign	0.2968	benign	-0.761	Destabilizing	0.457	N	0.456	neutral	N	0.50132732	None	None	N
E/F	0.9332	likely_pathogenic	0.9073	pathogenic	-0.662	Destabilizing	0.989	D	0.745	deleterious	None	None	None	None	N
E/G	0.3863	ambiguous	0.3462	ambiguous	-1.116	Destabilizing	0.003	N	0.392	neutral	N	0.47128159	None	None	N
E/H	0.7885	likely_pathogenic	0.6751	pathogenic	-0.838	Destabilizing	0.989	D	0.532	neutral	None	None	None	None	N
E/I	0.6102	likely_pathogenic	0.5445	ambiguous	-0.124	Destabilizing	0.888	D	0.777	deleterious	None	None	None	None	N
E/K	0.3516	ambiguous	0.2455	benign	-0.147	Destabilizing	0.457	N	0.609	neutral	N	0.449280803	None	None	N
E/L	0.6448	likely_pathogenic	0.6076	pathogenic	-0.124	Destabilizing	0.888	D	0.76	deleterious	None	None	None	None	N
E/M	0.6968	likely_pathogenic	0.6401	pathogenic	0.273	Stabilizing	0.989	D	0.722	deleterious	None	None	None	None	N
E/N	0.5633	ambiguous	0.5055	ambiguous	-0.502	Destabilizing	0.797	D	0.609	neutral	None	None	None	None	N
E/P	0.8534	likely_pathogenic	0.9434	pathogenic	-0.343	Destabilizing	0.888	D	0.569	neutral	None	None	None	None	N
E/Q	0.2448	likely_benign	0.1812	benign	-0.456	Destabilizing	0.857	D	0.624	neutral	N	0.469032826	None	None	N
E/R	0.5346	ambiguous	0.4004	ambiguous	-0.022	Destabilizing	0.888	D	0.584	neutral	None	None	None	None	N
E/S	0.3738	ambiguous	0.3243	benign	-0.741	Destabilizing	0.359	N	0.603	neutral	None	None	None	None	N
E/T	0.3951	ambiguous	0.302	benign	-0.515	Destabilizing	0.797	D	0.545	neutral	None	None	None	None	N
E/V	0.3955	ambiguous	0.3199	benign	-0.343	Destabilizing	0.857	D	0.7	prob.delet.	N	0.474232013	None	None	N
E/W	0.9801	likely_pathogenic	0.9721	pathogenic	-0.451	Destabilizing	0.989	D	0.781	deleterious	None	None	None	None	N
E/Y	0.9003	likely_pathogenic	0.8668	pathogenic	-0.406	Destabilizing	0.96	D	0.713	prob.delet.	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.