TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25623	77092;77093;77094	chr2:178569265;178569264;178569263	chr2:179433992;179433991;179433990
N2AB	23982	72169;72170;72171	chr2:178569265;178569264;178569263	chr2:179433992;179433991;179433990
N2A	23055	69388;69389;69390	chr2:178569265;178569264;178569263	chr2:179433992;179433991;179433990
N2B	16558	49897;49898;49899	chr2:178569265;178569264;178569263	chr2:179433992;179433991;179433990
Novex-1	16683	50272;50273;50274	chr2:178569265;178569264;178569263	chr2:179433992;179433991;179433990
Novex-2	16750	50473;50474;50475	chr2:178569265;178569264;178569263	chr2:179433992;179433991;179433990
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: Fn3-74
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4154
• 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
E/G	None	None	0.698	N	0.636	0.41	0.436671004673	gnomAD-4.0.0	1.61171E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89382E-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
E/A	0.2866	likely_benign	0.3049	benign	-0.694	Destabilizing	0.822	D	0.612	neutral	N	0.472662685	None	None	I
E/C	0.9081	likely_pathogenic	0.9203	pathogenic	-0.348	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	I
E/D	0.1113	likely_benign	0.1097	benign	-1.043	Destabilizing	0.014	N	0.228	neutral	N	0.432921474	None	None	I
E/F	0.8696	likely_pathogenic	0.8926	pathogenic	-0.457	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	I
E/G	0.3379	likely_benign	0.3489	ambiguous	-1.014	Destabilizing	0.698	D	0.636	neutral	N	0.485032949	None	None	I
E/H	0.6947	likely_pathogenic	0.7226	pathogenic	-0.769	Destabilizing	0.978	D	0.619	neutral	None	None	None	None	I
E/I	0.5273	ambiguous	0.5643	pathogenic	0.159	Stabilizing	0.978	D	0.779	deleterious	None	None	None	None	I
E/K	0.4176	ambiguous	0.4367	ambiguous	-0.657	Destabilizing	0.822	D	0.493	neutral	N	0.49383386	None	None	I
E/L	0.5208	ambiguous	0.5455	ambiguous	0.159	Stabilizing	0.978	D	0.77	deleterious	None	None	None	None	I
E/M	0.5542	ambiguous	0.5891	pathogenic	0.564	Stabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
E/N	0.3064	likely_benign	0.3217	benign	-0.919	Destabilizing	0.043	N	0.317	neutral	None	None	None	None	I
E/P	0.98	likely_pathogenic	0.9814	pathogenic	-0.104	Destabilizing	0.978	D	0.751	deleterious	None	None	None	None	I
E/Q	0.2307	likely_benign	0.2443	benign	-0.816	Destabilizing	0.942	D	0.605	neutral	N	0.518038872	None	None	I
E/R	0.6206	likely_pathogenic	0.6491	pathogenic	-0.435	Destabilizing	0.956	D	0.622	neutral	None	None	None	None	I
E/S	0.2839	likely_benign	0.303	benign	-1.195	Destabilizing	0.754	D	0.486	neutral	None	None	None	None	I
E/T	0.3532	ambiguous	0.3791	ambiguous	-0.949	Destabilizing	0.86	D	0.704	prob.neutral	None	None	None	None	I
E/V	0.3513	ambiguous	0.3804	ambiguous	-0.104	Destabilizing	0.971	D	0.772	deleterious	N	0.4760565	None	None	I
E/W	0.965	likely_pathogenic	0.9713	pathogenic	-0.342	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	I
E/Y	0.7616	likely_pathogenic	0.7878	pathogenic	-0.262	Destabilizing	0.993	D	0.782	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.