TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32296	97111;97112;97113	chr2:178543087;178543086;178543085	chr2:179407814;179407813;179407812
N2AB	30655	92188;92189;92190	chr2:178543087;178543086;178543085	chr2:179407814;179407813;179407812
N2A	29728	89407;89408;89409	chr2:178543087;178543086;178543085	chr2:179407814;179407813;179407812
N2B	23231	69916;69917;69918	chr2:178543087;178543086;178543085	chr2:179407814;179407813;179407812
Novex-1	23356	70291;70292;70293	chr2:178543087;178543086;178543085	chr2:179407814;179407813;179407812
Novex-2	23423	70492;70493;70494	chr2:178543087;178543086;178543085	chr2:179407814;179407813;179407812
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: Fn3-123
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.334
• 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
T/I	rs773279450	0.097	0.657	N	0.622	0.197	0.362960570912	gnomAD-4.0.0	1.38575E-06	None	None	None	None	N	None	3.01459E-05	0	None	0	0	None	0	0	9.09511E-07	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	0.0947	likely_benign	0.0911	benign	-0.672	Destabilizing	0.612	D	0.522	neutral	N	0.514889497	None	None	N
T/C	0.4415	ambiguous	0.427	ambiguous	-0.51	Destabilizing	0.998	D	0.707	prob.delet.	None	None	None	None	N
T/D	0.4986	ambiguous	0.4966	ambiguous	0.045	Stabilizing	0.973	D	0.618	neutral	None	None	None	None	N
T/E	0.3779	ambiguous	0.3746	ambiguous	0.038	Stabilizing	0.947	D	0.623	neutral	None	None	None	None	N
T/F	0.2673	likely_benign	0.2607	benign	-0.795	Destabilizing	0.973	D	0.795	deleterious	None	None	None	None	N
T/G	0.3761	ambiguous	0.3686	ambiguous	-0.912	Destabilizing	0.947	D	0.637	neutral	None	None	None	None	N
T/H	0.3045	likely_benign	0.2978	benign	-1.156	Destabilizing	0.993	D	0.733	deleterious	None	None	None	None	N
T/I	0.1195	likely_benign	0.1139	benign	-0.132	Destabilizing	0.657	D	0.622	neutral	N	0.485817384	None	None	N
T/K	0.2293	likely_benign	0.2374	benign	-0.578	Destabilizing	0.717	D	0.63	neutral	None	None	None	None	N
T/L	0.0864	likely_benign	0.0843	benign	-0.132	Destabilizing	0.717	D	0.547	neutral	None	None	None	None	N
T/M	0.082	likely_benign	0.0799	benign	0.018	Stabilizing	0.993	D	0.709	prob.delet.	None	None	None	None	N
T/N	0.1525	likely_benign	0.1512	benign	-0.533	Destabilizing	0.931	D	0.583	neutral	N	0.505195254	None	None	N
T/P	0.1275	likely_benign	0.1303	benign	-0.279	Destabilizing	0.988	D	0.693	prob.delet.	N	0.48658402	None	None	N
T/Q	0.2559	likely_benign	0.2544	benign	-0.688	Destabilizing	0.947	D	0.701	prob.delet.	None	None	None	None	N
T/R	0.1895	likely_benign	0.1955	benign	-0.348	Destabilizing	0.035	N	0.387	neutral	None	None	None	None	N
T/S	0.1525	likely_benign	0.1466	benign	-0.827	Destabilizing	0.792	D	0.496	neutral	N	0.47793674	None	None	N
T/V	0.1031	likely_benign	0.1008	benign	-0.279	Destabilizing	0.064	N	0.346	neutral	None	None	None	None	N
T/W	0.6047	likely_pathogenic	0.6095	pathogenic	-0.73	Destabilizing	0.998	D	0.725	deleterious	None	None	None	None	N
T/Y	0.3062	likely_benign	0.3117	benign	-0.483	Destabilizing	0.991	D	0.791	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.