TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32499	97720;97721;97722	chr2:178541582;178541581;178541580	chr2:179406309;179406308;179406307
N2AB	30858	92797;92798;92799	chr2:178541582;178541581;178541580	chr2:179406309;179406308;179406307
N2A	29931	90016;90017;90018	chr2:178541582;178541581;178541580	chr2:179406309;179406308;179406307
N2B	23434	70525;70526;70527	chr2:178541582;178541581;178541580	chr2:179406309;179406308;179406307
Novex-1	23559	70900;70901;70902	chr2:178541582;178541581;178541580	chr2:179406309;179406308;179406307
Novex-2	23626	71101;71102;71103	chr2:178541582;178541581;178541580	chr2:179406309;179406308;179406307
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: Fn3-125
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4741
• 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/T	None	None	0.115	N	0.525	0.301	0.592571446383	gnomAD-4.0.0	1.37649E-06	None	None	None	None	I	None	0	2.27097E-05	None	0	0	None	0	0	9.03664E-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
I/A	0.3943	ambiguous	0.2593	benign	-0.424	Destabilizing	0.034	N	0.456	neutral	None	None	None	None	I
I/C	0.6777	likely_pathogenic	0.5316	ambiguous	-0.758	Destabilizing	0.934	D	0.425	neutral	None	None	None	None	I
I/D	0.7222	likely_pathogenic	0.6067	pathogenic	-0.017	Destabilizing	0.552	D	0.657	prob.neutral	None	None	None	None	I
I/E	0.5287	ambiguous	0.4134	ambiguous	-0.111	Destabilizing	0.552	D	0.597	neutral	None	None	None	None	I
I/F	0.2621	likely_benign	0.1902	benign	-0.523	Destabilizing	0.314	N	0.344	neutral	N	0.500365549	None	None	I
I/G	0.6976	likely_pathogenic	0.5378	ambiguous	-0.543	Destabilizing	0.378	N	0.579	neutral	None	None	None	None	I
I/H	0.5999	likely_pathogenic	0.4437	ambiguous	0.104	Stabilizing	0.934	D	0.646	neutral	None	None	None	None	I
I/K	0.3917	ambiguous	0.2888	benign	-0.232	Destabilizing	0.378	N	0.587	neutral	None	None	None	None	I
I/L	0.1179	likely_benign	0.0847	benign	-0.238	Destabilizing	None	N	0.119	neutral	N	0.454051682	None	None	I
I/M	0.1328	likely_benign	0.0967	benign	-0.474	Destabilizing	0.004	N	0.397	neutral	N	0.480142467	None	None	I
I/N	0.2953	likely_benign	0.2201	benign	-0.103	Destabilizing	0.481	N	0.661	prob.neutral	N	0.480649446	None	None	I
I/P	0.3838	ambiguous	0.2685	benign	-0.27	Destabilizing	0.789	D	0.654	prob.neutral	None	None	None	None	I
I/Q	0.4357	ambiguous	0.3112	benign	-0.29	Destabilizing	0.378	N	0.654	prob.neutral	None	None	None	None	I
I/R	0.3606	ambiguous	0.2652	benign	0.235	Stabilizing	0.378	N	0.653	prob.neutral	None	None	None	None	I
I/S	0.3291	likely_benign	0.2471	benign	-0.531	Destabilizing	0.314	N	0.47	neutral	N	0.484934736	None	None	I
I/T	0.2666	likely_benign	0.185	benign	-0.517	Destabilizing	0.115	N	0.525	neutral	N	0.420403255	None	None	I
I/V	0.0861	likely_benign	0.0698	benign	-0.27	Destabilizing	0.002	N	0.176	neutral	N	0.401217275	None	None	I
I/W	0.8499	likely_pathogenic	0.7584	pathogenic	-0.537	Destabilizing	0.934	D	0.709	prob.delet.	None	None	None	None	I
I/Y	0.5548	ambiguous	0.4648	ambiguous	-0.286	Destabilizing	0.552	D	0.489	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.