TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25039	75340;75341;75342	chr2:178571017;178571016;178571015	chr2:179435744;179435743;179435742
N2AB	23398	70417;70418;70419	chr2:178571017;178571016;178571015	chr2:179435744;179435743;179435742
N2A	22471	67636;67637;67638	chr2:178571017;178571016;178571015	chr2:179435744;179435743;179435742
N2B	15974	48145;48146;48147	chr2:178571017;178571016;178571015	chr2:179435744;179435743;179435742
Novex-1	16099	48520;48521;48522	chr2:178571017;178571016;178571015	chr2:179435744;179435743;179435742
Novex-2	16166	48721;48722;48723	chr2:178571017;178571016;178571015	chr2:179435744;179435743;179435742
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: Fn3-70
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3649
• 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
T/A	rs1272032995	None	0.958	N	0.461	0.354	0.300784259202	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs1272032995	None	0.958	N	0.461	0.354	0.300784259202	gnomAD-4.0.0	2.0301E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40998E-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
T/A	0.2122	likely_benign	0.2252	benign	-0.859	Destabilizing	0.958	D	0.461	neutral	N	0.497047591	None	None	I
T/C	0.6784	likely_pathogenic	0.6954	pathogenic	-0.549	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
T/D	0.8544	likely_pathogenic	0.8608	pathogenic	-0.517	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	I
T/E	0.7636	likely_pathogenic	0.7938	pathogenic	-0.534	Destabilizing	0.995	D	0.779	deleterious	None	None	None	None	I
T/F	0.6233	likely_pathogenic	0.68	pathogenic	-1.065	Destabilizing	0.991	D	0.84	deleterious	None	None	None	None	I
T/G	0.6371	likely_pathogenic	0.6322	pathogenic	-1.086	Destabilizing	0.995	D	0.687	prob.neutral	None	None	None	None	I
T/H	0.7026	likely_pathogenic	0.733	pathogenic	-1.399	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
T/I	0.204	likely_benign	0.2804	benign	-0.351	Destabilizing	0.976	D	0.646	neutral	N	0.486545316	None	None	I
T/K	0.6541	likely_pathogenic	0.6916	pathogenic	-0.726	Destabilizing	0.995	D	0.744	deleterious	None	None	None	None	I
T/L	0.1833	likely_benign	0.2313	benign	-0.351	Destabilizing	0.086	N	0.313	neutral	None	None	None	None	I
T/M	0.1441	likely_benign	0.1653	benign	0.104	Stabilizing	0.998	D	0.807	deleterious	None	None	None	None	I
T/N	0.3688	ambiguous	0.4059	ambiguous	-0.667	Destabilizing	0.998	D	0.729	prob.delet.	N	0.482083661	None	None	I
T/P	0.7545	likely_pathogenic	0.7408	pathogenic	-0.49	Destabilizing	0.998	D	0.809	deleterious	D	0.526801321	None	None	I
T/Q	0.6033	likely_pathogenic	0.6345	pathogenic	-0.945	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	I
T/R	0.5794	likely_pathogenic	0.6064	pathogenic	-0.41	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	I
T/S	0.2527	likely_benign	0.2578	benign	-0.93	Destabilizing	0.979	D	0.453	neutral	N	0.469700171	None	None	I
T/V	0.1689	likely_benign	0.2171	benign	-0.49	Destabilizing	0.938	D	0.457	neutral	None	None	None	None	I
T/W	0.9007	likely_pathogenic	0.9132	pathogenic	-0.966	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
T/Y	0.7254	likely_pathogenic	0.76	pathogenic	-0.727	Destabilizing	0.995	D	0.843	deleterious	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.