TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20058	60397;60398;60399	chr2:178591647;178591646;178591645	chr2:179456374;179456373;179456372
N2AB	18417	55474;55475;55476	chr2:178591647;178591646;178591645	chr2:179456374;179456373;179456372
N2A	17490	52693;52694;52695	chr2:178591647;178591646;178591645	chr2:179456374;179456373;179456372
N2B	10993	33202;33203;33204	chr2:178591647;178591646;178591645	chr2:179456374;179456373;179456372
Novex-1	11118	33577;33578;33579	chr2:178591647;178591646;178591645	chr2:179456374;179456373;179456372
Novex-2	11185	33778;33779;33780	chr2:178591647;178591646;178591645	chr2:179456374;179456373;179456372
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-33
• Domain position: 82
• Structural Position: 117
• Q(SASA): 0.2914
• 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
L/F	rs2050227759	None	1.0	N	0.786	0.286	0.473774312618	gnomAD-4.0.0	1.59194E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85977E-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
L/A	0.1961	likely_benign	0.1793	benign	-1.286	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
L/C	0.4793	ambiguous	0.4919	ambiguous	-0.791	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
L/D	0.6268	likely_pathogenic	0.6353	pathogenic	-0.591	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
L/E	0.3037	likely_benign	0.2971	benign	-0.652	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
L/F	0.171	likely_benign	0.1721	benign	-1.055	Destabilizing	1.0	D	0.786	deleterious	N	0.496620662	None	None	I
L/G	0.5538	ambiguous	0.5483	ambiguous	-1.53	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
L/H	0.2702	likely_benign	0.2703	benign	-0.658	Destabilizing	1.0	D	0.811	deleterious	N	0.468073421	None	None	I
L/I	0.0975	likely_benign	0.1006	benign	-0.728	Destabilizing	0.999	D	0.6	neutral	N	0.45038694	None	None	I
L/K	0.2607	likely_benign	0.2573	benign	-0.724	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
L/M	0.1215	likely_benign	0.1211	benign	-0.545	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
L/N	0.3686	ambiguous	0.3807	ambiguous	-0.44	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
L/P	0.2035	likely_benign	0.1868	benign	-0.881	Destabilizing	1.0	D	0.818	deleterious	N	0.459006424	None	None	I
L/Q	0.174	likely_benign	0.1604	benign	-0.705	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
L/R	0.2253	likely_benign	0.2201	benign	-0.066	Destabilizing	1.0	D	0.821	deleterious	N	0.466087112	None	None	I
L/S	0.2645	likely_benign	0.2649	benign	-1.018	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
L/T	0.1614	likely_benign	0.1599	benign	-0.967	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
L/V	0.0953	likely_benign	0.0913	benign	-0.881	Destabilizing	0.999	D	0.648	neutral	N	0.427606081	None	None	I
L/W	0.299	likely_benign	0.3169	benign	-1.018	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
L/Y	0.3926	ambiguous	0.3946	ambiguous	-0.808	Destabilizing	1.0	D	0.794	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.