TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20065	60418;60419;60420	chr2:178591626;178591625;178591624	chr2:179456353;179456352;179456351
N2AB	18424	55495;55496;55497	chr2:178591626;178591625;178591624	chr2:179456353;179456352;179456351
N2A	17497	52714;52715;52716	chr2:178591626;178591625;178591624	chr2:179456353;179456352;179456351
N2B	11000	33223;33224;33225	chr2:178591626;178591625;178591624	chr2:179456353;179456352;179456351
Novex-1	11125	33598;33599;33600	chr2:178591626;178591625;178591624	chr2:179456353;179456352;179456351
Novex-2	11192	33799;33800;33801	chr2:178591626;178591625;178591624	chr2:179456353;179456352;179456351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-33
• Domain position: 89
• Structural Position: 125
• Q(SASA): 0.8388
• 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/L	None	None	0.001	N	0.117	0.118	0.369867359543	gnomAD-4.0.0	1.5923E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86008E-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	0.4231	ambiguous	0.4404	ambiguous	-0.825	Destabilizing	0.338	N	0.334	neutral	None	None	None	None	I
I/C	0.8176	likely_pathogenic	0.8446	pathogenic	-0.636	Destabilizing	0.995	D	0.349	neutral	None	None	None	None	I
I/D	0.7414	likely_pathogenic	0.7471	pathogenic	-0.669	Destabilizing	0.982	D	0.543	neutral	None	None	None	None	I
I/E	0.6326	likely_pathogenic	0.6398	pathogenic	-0.747	Destabilizing	0.946	D	0.481	neutral	None	None	None	None	I
I/F	0.2314	likely_benign	0.2349	benign	-0.767	Destabilizing	0.868	D	0.355	neutral	N	0.465529751	None	None	I
I/G	0.7066	likely_pathogenic	0.7231	pathogenic	-1.01	Destabilizing	0.946	D	0.477	neutral	None	None	None	None	I
I/H	0.6518	likely_pathogenic	0.6518	pathogenic	-0.244	Destabilizing	0.995	D	0.459	neutral	None	None	None	None	I
I/K	0.4806	ambiguous	0.4747	ambiguous	-0.604	Destabilizing	0.946	D	0.483	neutral	None	None	None	None	I
I/L	0.1188	likely_benign	0.1136	benign	-0.443	Destabilizing	0.001	N	0.117	neutral	N	0.394666944	None	None	I
I/M	0.1445	likely_benign	0.1417	benign	-0.497	Destabilizing	0.868	D	0.474	neutral	N	0.455102114	None	None	I
I/N	0.3876	ambiguous	0.3875	ambiguous	-0.394	Destabilizing	0.976	D	0.497	neutral	N	0.484635587	None	None	I
I/P	0.7022	likely_pathogenic	0.7199	pathogenic	-0.539	Destabilizing	0.982	D	0.536	neutral	None	None	None	None	I
I/Q	0.5359	ambiguous	0.54	ambiguous	-0.63	Destabilizing	0.982	D	0.483	neutral	None	None	None	None	I
I/R	0.4418	ambiguous	0.4409	ambiguous	0.018	Stabilizing	0.982	D	0.515	neutral	None	None	None	None	I
I/S	0.3727	ambiguous	0.3886	ambiguous	-0.789	Destabilizing	0.93	D	0.446	neutral	N	0.363037315	None	None	I
I/T	0.3502	ambiguous	0.3711	ambiguous	-0.761	Destabilizing	0.651	D	0.303	neutral	N	0.410348472	None	None	I
I/V	0.08	likely_benign	0.0812	benign	-0.539	Destabilizing	0.002	N	0.132	neutral	N	0.340851101	None	None	I
I/W	0.8604	likely_pathogenic	0.8556	pathogenic	-0.793	Destabilizing	0.995	D	0.539	neutral	None	None	None	None	I
I/Y	0.6176	likely_pathogenic	0.6405	pathogenic	-0.562	Destabilizing	0.982	D	0.4	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.