TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20734	62425;62426;62427	chr2:178589525;178589524;178589523	chr2:179454252;179454251;179454250
N2AB	19093	57502;57503;57504	chr2:178589525;178589524;178589523	chr2:179454252;179454251;179454250
N2A	18166	54721;54722;54723	chr2:178589525;178589524;178589523	chr2:179454252;179454251;179454250
N2B	11669	35230;35231;35232	chr2:178589525;178589524;178589523	chr2:179454252;179454251;179454250
Novex-1	11794	35605;35606;35607	chr2:178589525;178589524;178589523	chr2:179454252;179454251;179454250
Novex-2	11861	35806;35807;35808	chr2:178589525;178589524;178589523	chr2:179454252;179454251;179454250
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: Fn3-38
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4636
• 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	None	None	0.022	N	0.093	0.167	0.330331372229	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.1368	likely_benign	0.1816	benign	-1.328	Destabilizing	0.625	D	0.219	neutral	N	0.481731355	None	None	N
V/C	0.6704	likely_pathogenic	0.7598	pathogenic	-0.91	Destabilizing	0.998	D	0.347	neutral	None	None	None	None	N
V/D	0.3539	ambiguous	0.436	ambiguous	-0.929	Destabilizing	0.966	D	0.413	neutral	N	0.452448598	None	None	N
V/E	0.2301	likely_benign	0.2939	benign	-0.952	Destabilizing	0.949	D	0.353	neutral	None	None	None	None	N
V/F	0.1936	likely_benign	0.2476	benign	-1.084	Destabilizing	0.934	D	0.356	neutral	N	0.478269762	None	None	N
V/G	0.2294	likely_benign	0.2793	benign	-1.622	Destabilizing	0.891	D	0.368	neutral	N	0.466431261	None	None	N
V/H	0.4348	ambiguous	0.5326	ambiguous	-1.053	Destabilizing	0.037	N	0.347	neutral	None	None	None	None	N
V/I	0.0692	likely_benign	0.0814	benign	-0.639	Destabilizing	0.022	N	0.093	neutral	N	0.374950606	None	None	N
V/K	0.2514	likely_benign	0.292	benign	-1.053	Destabilizing	0.949	D	0.355	neutral	None	None	None	None	N
V/L	0.1386	likely_benign	0.1793	benign	-0.639	Destabilizing	0.005	N	0.069	neutral	N	0.439095298	None	None	N
V/M	0.1116	likely_benign	0.1651	benign	-0.489	Destabilizing	0.325	N	0.193	neutral	None	None	None	None	N
V/N	0.2045	likely_benign	0.2604	benign	-0.794	Destabilizing	0.949	D	0.41	neutral	None	None	None	None	N
V/P	0.6743	likely_pathogenic	0.6752	pathogenic	-0.833	Destabilizing	0.991	D	0.385	neutral	None	None	None	None	N
V/Q	0.2153	likely_benign	0.2572	benign	-0.984	Destabilizing	0.949	D	0.389	neutral	None	None	None	None	N
V/R	0.2597	likely_benign	0.2893	benign	-0.493	Destabilizing	0.949	D	0.405	neutral	None	None	None	None	N
V/S	0.1652	likely_benign	0.2074	benign	-1.332	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	N
V/T	0.1194	likely_benign	0.1681	benign	-1.24	Destabilizing	0.915	D	0.19	neutral	None	None	None	None	N
V/W	0.7833	likely_pathogenic	0.8716	pathogenic	-1.208	Destabilizing	0.998	D	0.442	neutral	None	None	None	None	N
V/Y	0.5317	ambiguous	0.634	pathogenic	-0.932	Destabilizing	0.949	D	0.363	neutral	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.