TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7360	22303;22304;22305	chr2:178722821;178722820;178722819	chr2:179587548;179587547;179587546
N2AB	7043	21352;21353;21354	chr2:178722821;178722820;178722819	chr2:179587548;179587547;179587546
N2A	6116	18571;18572;18573	chr2:178722821;178722820;178722819	chr2:179587548;179587547;179587546
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-58
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.814
• 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
D/V	None	None	0.999	N	0.563	0.487	0.541875726618	gnomAD-4.0.0	1.36879E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-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
D/A	0.1534	likely_benign	0.2443	benign	-0.015	Destabilizing	0.989	D	0.425	neutral	N	0.49530558	None	None	N
D/C	0.6037	likely_pathogenic	0.7841	pathogenic	-0.129	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	N
D/E	0.1437	likely_benign	0.2053	benign	-0.346	Destabilizing	0.989	D	0.45	neutral	N	0.465636034	None	None	N
D/F	0.448	ambiguous	0.6397	pathogenic	-0.101	Destabilizing	1.0	D	0.543	neutral	None	None	None	None	N
D/G	0.1268	likely_benign	0.1991	benign	-0.113	Destabilizing	0.217	N	0.283	neutral	N	0.37335223	None	None	N
D/H	0.2488	likely_benign	0.3817	ambiguous	0.492	Stabilizing	1.0	D	0.445	neutral	N	0.50642665	None	None	N
D/I	0.2819	likely_benign	0.4613	ambiguous	0.178	Stabilizing	1.0	D	0.567	neutral	None	None	None	None	N
D/K	0.3035	likely_benign	0.4553	ambiguous	0.445	Stabilizing	0.998	D	0.465	neutral	None	None	None	None	N
D/L	0.3308	likely_benign	0.4868	ambiguous	0.178	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
D/M	0.4979	ambiguous	0.6774	pathogenic	0.023	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	N
D/N	0.08	likely_benign	0.107	benign	0.177	Stabilizing	0.733	D	0.291	neutral	N	0.468521623	None	None	N
D/P	0.5889	likely_pathogenic	0.7696	pathogenic	0.132	Stabilizing	1.0	D	0.458	neutral	None	None	None	None	N
D/Q	0.2875	likely_benign	0.437	ambiguous	0.181	Stabilizing	0.999	D	0.446	neutral	None	None	None	None	N
D/R	0.3436	ambiguous	0.4984	ambiguous	0.639	Stabilizing	0.999	D	0.471	neutral	None	None	None	None	N
D/S	0.1157	likely_benign	0.1684	benign	0.103	Stabilizing	0.992	D	0.413	neutral	None	None	None	None	N
D/T	0.2082	likely_benign	0.3369	benign	0.191	Stabilizing	0.998	D	0.457	neutral	None	None	None	None	N
D/V	0.1882	likely_benign	0.3026	benign	0.132	Stabilizing	0.999	D	0.563	neutral	N	0.482002804	None	None	N
D/W	0.8364	likely_pathogenic	0.925	pathogenic	-0.059	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
D/Y	0.1892	likely_benign	0.2877	benign	0.12	Stabilizing	1.0	D	0.543	neutral	N	0.470393009	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.