TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21129	63610;63611;63612	chr2:178588022;178588021;178588020	chr2:179452749;179452748;179452747
N2AB	19488	58687;58688;58689	chr2:178588022;178588021;178588020	chr2:179452749;179452748;179452747
N2A	18561	55906;55907;55908	chr2:178588022;178588021;178588020	chr2:179452749;179452748;179452747
N2B	12064	36415;36416;36417	chr2:178588022;178588021;178588020	chr2:179452749;179452748;179452747
Novex-1	12189	36790;36791;36792	chr2:178588022;178588021;178588020	chr2:179452749;179452748;179452747
Novex-2	12256	36991;36992;36993	chr2:178588022;178588021;178588020	chr2:179452749;179452748;179452747
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: Fn3-41
• Domain position: 66
• Structural Position: 90
• Q(SASA): 0.4263
• 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/K	rs2049409124	None	0.885	N	0.449	0.242	0.273938319068	gnomAD-4.0.0	1.59314E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86118E-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	0.2567	likely_benign	0.3257	benign	-0.45	Destabilizing	0.939	D	0.505	neutral	N	0.491044271	None	None	I
E/C	0.8776	likely_pathogenic	0.9049	pathogenic	-0.306	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
E/D	0.2388	likely_benign	0.2508	benign	-0.943	Destabilizing	0.939	D	0.435	neutral	N	0.468027876	None	None	I
E/F	0.8504	likely_pathogenic	0.8726	pathogenic	0.436	Stabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	I
E/G	0.3542	ambiguous	0.4227	ambiguous	-0.862	Destabilizing	0.982	D	0.655	neutral	N	0.474927183	None	None	I
E/H	0.6152	likely_pathogenic	0.6543	pathogenic	0.319	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	I
E/I	0.4525	ambiguous	0.5216	ambiguous	0.685	Stabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	I
E/K	0.3861	ambiguous	0.4444	ambiguous	-0.325	Destabilizing	0.885	D	0.449	neutral	N	0.4978556	None	None	I
E/L	0.6216	likely_pathogenic	0.6791	pathogenic	0.685	Stabilizing	0.986	D	0.677	prob.neutral	None	None	None	None	I
E/M	0.5838	likely_pathogenic	0.6392	pathogenic	0.958	Stabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
E/N	0.4056	ambiguous	0.4512	ambiguous	-1.026	Destabilizing	0.986	D	0.617	neutral	None	None	None	None	I
E/P	0.9411	likely_pathogenic	0.9569	pathogenic	0.329	Stabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	I
E/Q	0.2001	likely_benign	0.2297	benign	-0.812	Destabilizing	0.17	N	0.421	neutral	N	0.514209133	None	None	I
E/R	0.4858	ambiguous	0.5384	ambiguous	0.028	Stabilizing	0.973	D	0.615	neutral	None	None	None	None	I
E/S	0.3095	likely_benign	0.3642	ambiguous	-1.345	Destabilizing	0.953	D	0.511	neutral	None	None	None	None	I
E/T	0.273	likely_benign	0.3254	benign	-0.983	Destabilizing	0.986	D	0.661	neutral	None	None	None	None	I
E/V	0.2629	likely_benign	0.3231	benign	0.329	Stabilizing	0.991	D	0.665	neutral	N	0.476991098	None	None	I
E/W	0.9471	likely_pathogenic	0.9532	pathogenic	0.706	Stabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
E/Y	0.7245	likely_pathogenic	0.7573	pathogenic	0.721	Stabilizing	0.998	D	0.721	prob.delet.	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.