TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24867	74824;74825;74826	chr2:178571533;178571532;178571531	chr2:179436260;179436259;179436258
N2AB	23226	69901;69902;69903	chr2:178571533;178571532;178571531	chr2:179436260;179436259;179436258
N2A	22299	67120;67121;67122	chr2:178571533;178571532;178571531	chr2:179436260;179436259;179436258
N2B	15802	47629;47630;47631	chr2:178571533;178571532;178571531	chr2:179436260;179436259;179436258
Novex-1	15927	48004;48005;48006	chr2:178571533;178571532;178571531	chr2:179436260;179436259;179436258
Novex-2	15994	48205;48206;48207	chr2:178571533;178571532;178571531	chr2:179436260;179436259;179436258
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: Fn3-68
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.1611
• 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/R	None	None	0.988	D	0.723	0.353	0.625243557465	gnomAD-4.0.0	1.203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31565E-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	0.1165	likely_benign	0.1065	benign	-0.972	Destabilizing	0.825	D	0.483	neutral	N	0.506976516	None	None	N
T/C	0.5281	ambiguous	0.4484	ambiguous	-0.508	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/D	0.7309	likely_pathogenic	0.6808	pathogenic	-0.309	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	N
T/E	0.5768	likely_pathogenic	0.5283	ambiguous	-0.192	Destabilizing	0.991	D	0.672	neutral	None	None	None	None	N
T/F	0.4384	ambiguous	0.3671	ambiguous	-0.778	Destabilizing	0.995	D	0.792	deleterious	None	None	None	None	N
T/G	0.4081	ambiguous	0.3608	ambiguous	-1.338	Destabilizing	0.938	D	0.583	neutral	None	None	None	None	N
T/H	0.4198	ambiguous	0.3667	ambiguous	-1.429	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/I	0.332	likely_benign	0.2361	benign	-0.049	Destabilizing	0.994	D	0.721	prob.delet.	N	0.484374612	None	None	N
T/K	0.3966	ambiguous	0.3654	ambiguous	-0.445	Destabilizing	0.988	D	0.679	prob.neutral	N	0.521695252	None	None	N
T/L	0.1812	likely_benign	0.1493	benign	-0.049	Destabilizing	0.968	D	0.593	neutral	None	None	None	None	N
T/M	0.115	likely_benign	0.1	benign	0.014	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/N	0.2196	likely_benign	0.1881	benign	-0.757	Destabilizing	0.991	D	0.672	neutral	None	None	None	None	N
T/P	0.8861	likely_pathogenic	0.8701	pathogenic	-0.323	Destabilizing	0.994	D	0.725	prob.delet.	N	0.476385668	None	None	N
T/Q	0.3275	likely_benign	0.3026	benign	-0.671	Destabilizing	0.991	D	0.758	deleterious	None	None	None	None	N
T/R	0.3614	ambiguous	0.3244	benign	-0.47	Destabilizing	0.988	D	0.723	prob.delet.	D	0.522540614	None	None	N
T/S	0.1348	likely_benign	0.1194	benign	-1.105	Destabilizing	0.234	N	0.435	neutral	N	0.440922095	None	None	N
T/V	0.1877	likely_benign	0.1467	benign	-0.323	Destabilizing	0.968	D	0.554	neutral	None	None	None	None	N
T/W	0.8247	likely_pathogenic	0.7758	pathogenic	-0.792	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/Y	0.5048	ambiguous	0.4457	ambiguous	-0.483	Destabilizing	0.998	D	0.796	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.