TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20950	63073;63074;63075	chr2:178588877;178588876;178588875	chr2:179453604;179453603;179453602
N2AB	19309	58150;58151;58152	chr2:178588877;178588876;178588875	chr2:179453604;179453603;179453602
N2A	18382	55369;55370;55371	chr2:178588877;178588876;178588875	chr2:179453604;179453603;179453602
N2B	11885	35878;35879;35880	chr2:178588877;178588876;178588875	chr2:179453604;179453603;179453602
Novex-1	12010	36253;36254;36255	chr2:178588877;178588876;178588875	chr2:179453604;179453603;179453602
Novex-2	12077	36454;36455;36456	chr2:178588877;178588876;178588875	chr2:179453604;179453603;179453602
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-39
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1491
• 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/A	rs748774963	-1.138	0.349	N	0.735	0.072	0.218112801441	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	1.12397E-04	None	0	None	0	0	0
T/A	rs748774963	-1.138	0.349	N	0.735	0.072	0.218112801441	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94024E-04	None	0	0	0	0	0
T/A	rs748774963	-1.138	0.349	N	0.735	0.072	0.218112801441	gnomAD-4.0.0	1.28176E-05	None	None	None	None	N	None	0	0	None	0	2.19223E-04	None	0	0	2.39412E-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
T/A	0.0682	likely_benign	0.0645	benign	-0.992	Destabilizing	0.349	N	0.735	prob.delet.	N	0.461268443	None	None	N
T/C	0.2419	likely_benign	0.2589	benign	-0.756	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
T/D	0.6531	likely_pathogenic	0.594	pathogenic	-0.583	Destabilizing	0.987	D	0.835	deleterious	None	None	None	None	N
T/E	0.3936	ambiguous	0.3192	benign	-0.486	Destabilizing	0.961	D	0.841	deleterious	None	None	None	None	N
T/F	0.2676	likely_benign	0.2767	benign	-0.678	Destabilizing	0.923	D	0.868	deleterious	None	None	None	None	N
T/G	0.2789	likely_benign	0.2742	benign	-1.345	Destabilizing	0.961	D	0.841	deleterious	None	None	None	None	N
T/H	0.3923	ambiguous	0.3719	ambiguous	-1.489	Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
T/I	0.119	likely_benign	0.1128	benign	-0.108	Destabilizing	0.309	N	0.774	deleterious	N	0.51248391	None	None	N
T/K	0.3362	likely_benign	0.2675	benign	-0.787	Destabilizing	0.949	D	0.837	deleterious	N	0.47733131	None	None	N
T/L	0.0897	likely_benign	0.0876	benign	-0.108	Destabilizing	0.415	N	0.737	prob.delet.	None	None	None	None	N
T/M	0.0798	likely_benign	0.0801	benign	-0.079	Destabilizing	0.237	N	0.669	neutral	None	None	None	None	N
T/N	0.2384	likely_benign	0.2275	benign	-0.996	Destabilizing	0.987	D	0.794	deleterious	None	None	None	None	N
T/P	0.8217	likely_pathogenic	0.8126	pathogenic	-0.37	Destabilizing	0.983	D	0.839	deleterious	N	0.478091779	None	None	N
T/Q	0.2696	likely_benign	0.2387	benign	-0.978	Destabilizing	0.961	D	0.832	deleterious	None	None	None	None	N
T/R	0.2807	likely_benign	0.2254	benign	-0.75	Destabilizing	0.949	D	0.833	deleterious	N	0.489105689	None	None	N
T/S	0.1302	likely_benign	0.1322	benign	-1.301	Destabilizing	0.722	D	0.767	deleterious	N	0.41518665	None	None	N
T/V	0.0768	likely_benign	0.0753	benign	-0.37	Destabilizing	0.005	N	0.47	neutral	None	None	None	None	N
T/W	0.706	likely_pathogenic	0.7067	pathogenic	-0.661	Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	N
T/Y	0.3871	ambiguous	0.3536	ambiguous	-0.394	Destabilizing	0.961	D	0.873	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.