TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17230	51913;51914;51915	chr2:178609735;178609734;178609733	chr2:179474462;179474461;179474460
N2AB	15589	46990;46991;46992	chr2:178609735;178609734;178609733	chr2:179474462;179474461;179474460
N2A	14662	44209;44210;44211	chr2:178609735;178609734;178609733	chr2:179474462;179474461;179474460
N2B	8165	24718;24719;24720	chr2:178609735;178609734;178609733	chr2:179474462;179474461;179474460
Novex-1	8290	25093;25094;25095	chr2:178609735;178609734;178609733	chr2:179474462;179474461;179474460
Novex-2	8357	25294;25295;25296	chr2:178609735;178609734;178609733	chr2:179474462;179474461;179474460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-13
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3271
• 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
I/V	None	None	0.002	N	0.207	0.067	0.241664281697	gnomAD-4.0.0	1.59666E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87031E-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
I/A	0.2834	likely_benign	0.3168	benign	-1.511	Destabilizing	0.525	D	0.539	neutral	None	None	None	None	I
I/C	0.6134	likely_pathogenic	0.6455	pathogenic	-1.102	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	I
I/D	0.7119	likely_pathogenic	0.7335	pathogenic	-0.503	Destabilizing	0.991	D	0.688	prob.neutral	None	None	None	None	I
I/E	0.5398	ambiguous	0.5857	pathogenic	-0.52	Destabilizing	0.974	D	0.685	prob.neutral	None	None	None	None	I
I/F	0.1788	likely_benign	0.1791	benign	-1.126	Destabilizing	0.934	D	0.609	neutral	N	0.463065449	None	None	I
I/G	0.6318	likely_pathogenic	0.6545	pathogenic	-1.798	Destabilizing	0.974	D	0.677	prob.neutral	None	None	None	None	I
I/H	0.5811	likely_pathogenic	0.6221	pathogenic	-0.84	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I
I/K	0.4593	ambiguous	0.4963	ambiguous	-0.795	Destabilizing	0.974	D	0.683	prob.neutral	None	None	None	None	I
I/L	0.1122	likely_benign	0.1176	benign	-0.818	Destabilizing	0.267	N	0.275	neutral	N	0.367749701	None	None	I
I/M	0.1177	likely_benign	0.1245	benign	-0.711	Destabilizing	0.267	N	0.307	neutral	N	0.444826405	None	None	I
I/N	0.3084	likely_benign	0.3411	ambiguous	-0.606	Destabilizing	0.989	D	0.693	prob.neutral	N	0.457408913	None	None	I
I/P	0.5235	ambiguous	0.5957	pathogenic	-1.016	Destabilizing	0.991	D	0.69	prob.neutral	None	None	None	None	I
I/Q	0.4674	ambiguous	0.5123	ambiguous	-0.819	Destabilizing	0.974	D	0.692	prob.neutral	None	None	None	None	I
I/R	0.411	ambiguous	0.4365	ambiguous	-0.198	Destabilizing	0.974	D	0.685	prob.neutral	None	None	None	None	I
I/S	0.2951	likely_benign	0.314	benign	-1.316	Destabilizing	0.891	D	0.674	neutral	N	0.44018859	None	None	I
I/T	0.2008	likely_benign	0.236	benign	-1.211	Destabilizing	0.801	D	0.546	neutral	N	0.430665029	None	None	I
I/V	0.0637	likely_benign	0.0694	benign	-1.016	Destabilizing	0.002	N	0.207	neutral	N	0.36792306	None	None	I
I/W	0.8199	likely_pathogenic	0.812	pathogenic	-1.073	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	I
I/Y	0.5508	ambiguous	0.5574	ambiguous	-0.858	Destabilizing	0.974	D	0.625	neutral	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.