TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19969	60130;60131;60132	chr2:178591999;178591998;178591997	chr2:179456726;179456725;179456724
N2AB	18328	55207;55208;55209	chr2:178591999;178591998;178591997	chr2:179456726;179456725;179456724
N2A	17401	52426;52427;52428	chr2:178591999;178591998;178591997	chr2:179456726;179456725;179456724
N2B	10904	32935;32936;32937	chr2:178591999;178591998;178591997	chr2:179456726;179456725;179456724
Novex-1	11029	33310;33311;33312	chr2:178591999;178591998;178591997	chr2:179456726;179456725;179456724
Novex-2	11096	33511;33512;33513	chr2:178591999;178591998;178591997	chr2:179456726;179456725;179456724
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: Fn3-32
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.1891
• 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
I/V	rs1232358158	-1.214	0.881	N	0.431	0.069	0.43965937752	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	4.65E-05	8.93E-06	0
I/V	rs1232358158	-1.214	0.881	N	0.431	0.069	0.43965937752	gnomAD-4.0.0	3.42329E-06	None	None	None	None	N	None	0	2.24296E-05	None	0	0	None	3.74784E-05	0	1.79945E-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	0.5999	likely_pathogenic	0.6066	pathogenic	-2.237	Highly Destabilizing	0.982	D	0.599	neutral	None	None	None	None	N
I/C	0.7541	likely_pathogenic	0.7629	pathogenic	-1.368	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
I/D	0.9638	likely_pathogenic	0.9755	pathogenic	-2.466	Highly Destabilizing	0.997	D	0.806	deleterious	None	None	None	None	N
I/E	0.8341	likely_pathogenic	0.8764	pathogenic	-2.277	Highly Destabilizing	0.997	D	0.797	deleterious	None	None	None	None	N
I/F	0.2705	likely_benign	0.2677	benign	-1.354	Destabilizing	0.999	D	0.626	neutral	N	0.506202938	None	None	N
I/G	0.8896	likely_pathogenic	0.8948	pathogenic	-2.716	Highly Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
I/H	0.8011	likely_pathogenic	0.8347	pathogenic	-1.936	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/K	0.6841	likely_pathogenic	0.7462	pathogenic	-1.803	Destabilizing	0.997	D	0.806	deleterious	None	None	None	None	N
I/L	0.1559	likely_benign	0.1524	benign	-0.877	Destabilizing	0.944	D	0.454	neutral	N	0.504642713	None	None	N
I/M	0.16	likely_benign	0.156	benign	-0.683	Destabilizing	0.999	D	0.563	neutral	N	0.487867893	None	None	N
I/N	0.7516	likely_pathogenic	0.8178	pathogenic	-2.085	Highly Destabilizing	0.997	D	0.846	deleterious	N	0.506723013	None	None	N
I/P	0.9685	likely_pathogenic	0.976	pathogenic	-1.31	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
I/Q	0.6807	likely_pathogenic	0.7353	pathogenic	-2.027	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
I/R	0.6129	likely_pathogenic	0.6898	pathogenic	-1.396	Destabilizing	0.997	D	0.846	deleterious	None	None	None	None	N
I/S	0.6782	likely_pathogenic	0.7261	pathogenic	-2.714	Highly Destabilizing	0.954	D	0.733	deleterious	N	0.505856221	None	None	N
I/T	0.4505	ambiguous	0.5191	ambiguous	-2.387	Highly Destabilizing	0.355	N	0.395	neutral	N	0.505682863	None	None	N
I/V	0.066	likely_benign	0.0641	benign	-1.31	Destabilizing	0.881	D	0.431	neutral	N	0.455734045	None	None	N
I/W	0.881	likely_pathogenic	0.8977	pathogenic	-1.666	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
I/Y	0.7239	likely_pathogenic	0.7624	pathogenic	-1.354	Destabilizing	0.999	D	0.708	prob.delet.	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.