TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8826	26701;26702;26703	chr2:178714298;178714297;178714296	chr2:179579025;179579024;179579023
N2AB	8509	25750;25751;25752	chr2:178714298;178714297;178714296	chr2:179579025;179579024;179579023
N2A	7582	22969;22970;22971	chr2:178714298;178714297;178714296	chr2:179579025;179579024;179579023
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-73
• Domain position: 91
• Structural Position: 178
• Q(SASA): 0.2751
• 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
V/I	rs200116046	-0.82	0.001	N	0.471	0.258	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
V/I	rs200116046	-0.82	0.001	N	0.471	0.258	None	gnomAD-4.0.0	2.74088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70241E-06	1.16085E-05	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
V/A	0.4163	ambiguous	0.4988	ambiguous	-1.573	Destabilizing	0.298	N	0.616	neutral	D	0.631519556	None	None	N
V/C	0.8357	likely_pathogenic	0.8864	pathogenic	-1.256	Destabilizing	0.979	D	0.723	prob.delet.	None	None	None	None	N
V/D	0.8927	likely_pathogenic	0.9324	pathogenic	-1.11	Destabilizing	0.881	D	0.74	deleterious	D	0.632124969	None	None	N
V/E	0.8153	likely_pathogenic	0.8669	pathogenic	-1.071	Destabilizing	0.615	D	0.713	prob.delet.	None	None	None	None	N
V/F	0.3268	likely_benign	0.4019	ambiguous	-1.164	Destabilizing	0.875	D	0.725	prob.delet.	D	0.631519556	None	None	N
V/G	0.6087	likely_pathogenic	0.6804	pathogenic	-1.92	Destabilizing	0.91	D	0.725	prob.delet.	D	0.632124969	None	None	N
V/H	0.9141	likely_pathogenic	0.9488	pathogenic	-1.434	Destabilizing	0.984	D	0.725	prob.delet.	None	None	None	None	N
V/I	0.0654	likely_benign	0.0733	benign	-0.706	Destabilizing	0.001	N	0.471	neutral	N	0.504763268	None	None	N
V/K	0.867	likely_pathogenic	0.9079	pathogenic	-1.131	Destabilizing	0.777	D	0.713	prob.delet.	None	None	None	None	N
V/L	0.1854	likely_benign	0.2544	benign	-0.706	Destabilizing	0.012	N	0.641	neutral	D	0.629501513	None	None	N
V/M	0.221	likely_benign	0.2787	benign	-0.705	Destabilizing	0.724	D	0.731	prob.delet.	None	None	None	None	N
V/N	0.7115	likely_pathogenic	0.8093	pathogenic	-1.001	Destabilizing	0.611	D	0.745	deleterious	None	None	None	None	N
V/P	0.8205	likely_pathogenic	0.8626	pathogenic	-0.961	Destabilizing	0.611	D	0.72	prob.delet.	None	None	None	None	N
V/Q	0.8235	likely_pathogenic	0.8748	pathogenic	-1.116	Destabilizing	0.883	D	0.729	prob.delet.	None	None	None	None	N
V/R	0.8127	likely_pathogenic	0.8674	pathogenic	-0.76	Destabilizing	0.881	D	0.743	deleterious	None	None	None	None	N
V/S	0.5612	ambiguous	0.6526	pathogenic	-1.645	Destabilizing	0.8	D	0.695	prob.neutral	None	None	None	None	N
V/T	0.4699	ambiguous	0.5466	ambiguous	-1.487	Destabilizing	0.185	N	0.699	prob.neutral	None	None	None	None	N
V/W	0.9446	likely_pathogenic	0.9677	pathogenic	-1.336	Destabilizing	0.996	D	0.686	prob.neutral	None	None	None	None	N
V/Y	0.7997	likely_pathogenic	0.8667	pathogenic	-1.02	Destabilizing	0.881	D	0.727	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.