TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14972	45139;45140;45141	chr2:178622008;178622007;178622006	chr2:179486735;179486734;179486733
N2AB	13331	40216;40217;40218	chr2:178622008;178622007;178622006	chr2:179486735;179486734;179486733
N2A	12404	37435;37436;37437	chr2:178622008;178622007;178622006	chr2:179486735;179486734;179486733
N2B	5907	17944;17945;17946	chr2:178622008;178622007;178622006	chr2:179486735;179486734;179486733
Novex-1	6032	18319;18320;18321	chr2:178622008;178622007;178622006	chr2:179486735;179486734;179486733
Novex-2	6099	18520;18521;18522	chr2:178622008;178622007;178622006	chr2:179486735;179486734;179486733
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-101
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.2488
• 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/F	None	None	0.991	D	0.729	0.592	0.809165052584	gnomAD-4.0.0	6.90004E-07	None	None	None	None	N	None	0	0	None	0	2.55337E-05	None	0	0	0	0	0
V/I	None	None	0.863	D	0.547	0.314	0.620746667299	gnomAD-4.0.0	6.90004E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04743E-07	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	0.5069	ambiguous	0.4741	ambiguous	-1.475	Destabilizing	0.046	N	0.314	neutral	D	0.660556922	None	None	N
V/C	0.9119	likely_pathogenic	0.9001	pathogenic	-0.87	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
V/D	0.9029	likely_pathogenic	0.9032	pathogenic	-1.606	Destabilizing	0.991	D	0.788	deleterious	D	0.782780269	None	None	N
V/E	0.8524	likely_pathogenic	0.8614	pathogenic	-1.529	Destabilizing	0.986	D	0.785	deleterious	None	None	None	None	N
V/F	0.5735	likely_pathogenic	0.5343	ambiguous	-0.981	Destabilizing	0.991	D	0.729	prob.delet.	D	0.666968894	None	None	N
V/G	0.5193	ambiguous	0.5011	ambiguous	-1.847	Destabilizing	0.964	D	0.763	deleterious	D	0.611558875	None	None	N
V/H	0.9718	likely_pathogenic	0.97	pathogenic	-1.346	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/I	0.1403	likely_benign	0.1354	benign	-0.521	Destabilizing	0.863	D	0.547	neutral	D	0.524127032	None	None	N
V/K	0.9402	likely_pathogenic	0.9429	pathogenic	-1.304	Destabilizing	0.986	D	0.784	deleterious	None	None	None	None	N
V/L	0.5912	likely_pathogenic	0.5635	ambiguous	-0.521	Destabilizing	0.863	D	0.578	neutral	D	0.619365354	None	None	N
V/M	0.5343	ambiguous	0.5	ambiguous	-0.414	Destabilizing	0.998	D	0.702	prob.neutral	None	None	None	None	N
V/N	0.8758	likely_pathogenic	0.8807	pathogenic	-1.266	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
V/P	0.7437	likely_pathogenic	0.7612	pathogenic	-0.807	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/Q	0.9079	likely_pathogenic	0.9082	pathogenic	-1.331	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
V/R	0.927	likely_pathogenic	0.9298	pathogenic	-0.859	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/S	0.7489	likely_pathogenic	0.7345	pathogenic	-1.762	Destabilizing	0.973	D	0.764	deleterious	None	None	None	None	N
V/T	0.6021	likely_pathogenic	0.592	pathogenic	-1.567	Destabilizing	0.953	D	0.605	neutral	None	None	None	None	N
V/W	0.9747	likely_pathogenic	0.9701	pathogenic	-1.29	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
V/Y	0.9117	likely_pathogenic	0.9059	pathogenic	-0.938	Destabilizing	0.998	D	0.72	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.