TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20844	62755;62756;62757	chr2:178589195;178589194;178589193	chr2:179453922;179453921;179453920
N2AB	19203	57832;57833;57834	chr2:178589195;178589194;178589193	chr2:179453922;179453921;179453920
N2A	18276	55051;55052;55053	chr2:178589195;178589194;178589193	chr2:179453922;179453921;179453920
N2B	11779	35560;35561;35562	chr2:178589195;178589194;178589193	chr2:179453922;179453921;179453920
Novex-1	11904	35935;35936;35937	chr2:178589195;178589194;178589193	chr2:179453922;179453921;179453920
Novex-2	11971	36136;36137;36138	chr2:178589195;178589194;178589193	chr2:179453922;179453921;179453920
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-122
• Domain position: 76
• Structural Position: 156
• Q(SASA): 0.1032
• 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/A	rs775731244	-2.275	0.104	N	0.693	0.263	0.386882687439	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/A	rs775731244	-2.275	0.104	N	0.693	0.263	0.386882687439	gnomAD-4.0.0	2.73721E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63768E-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	0.8227	likely_pathogenic	0.8191	pathogenic	-1.807	Destabilizing	0.104	N	0.693	prob.neutral	N	0.492169274	None	None	N
V/C	0.9197	likely_pathogenic	0.9354	pathogenic	-1.207	Destabilizing	0.968	D	0.746	deleterious	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9982	pathogenic	-2.565	Highly Destabilizing	0.667	D	0.871	deleterious	N	0.48201603	None	None	N
V/E	0.9939	likely_pathogenic	0.9934	pathogenic	-2.366	Highly Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
V/F	0.728	likely_pathogenic	0.7222	pathogenic	-1.045	Destabilizing	0.497	N	0.761	deleterious	N	0.462555422	None	None	N
V/G	0.9553	likely_pathogenic	0.9523	pathogenic	-2.318	Highly Destabilizing	0.667	D	0.866	deleterious	N	0.481762541	None	None	N
V/H	0.9973	likely_pathogenic	0.9973	pathogenic	-2.198	Highly Destabilizing	0.968	D	0.869	deleterious	None	None	None	None	N
V/I	0.056	likely_benign	0.0558	benign	-0.394	Destabilizing	None	N	0.309	neutral	N	0.394794656	None	None	N
V/K	0.9942	likely_pathogenic	0.9936	pathogenic	-1.584	Destabilizing	0.726	D	0.84	deleterious	None	None	None	None	N
V/L	0.2203	likely_benign	0.2108	benign	-0.394	Destabilizing	0.009	N	0.403	neutral	N	0.433504973	None	None	N
V/M	0.4182	ambiguous	0.4351	ambiguous	-0.352	Destabilizing	0.567	D	0.663	neutral	None	None	None	None	N
V/N	0.9916	likely_pathogenic	0.9915	pathogenic	-1.841	Destabilizing	0.89	D	0.869	deleterious	None	None	None	None	N
V/P	0.9938	likely_pathogenic	0.9933	pathogenic	-0.837	Destabilizing	0.89	D	0.84	deleterious	None	None	None	None	N
V/Q	0.9912	likely_pathogenic	0.9904	pathogenic	-1.713	Destabilizing	0.89	D	0.859	deleterious	None	None	None	None	N
V/R	0.9901	likely_pathogenic	0.9886	pathogenic	-1.404	Destabilizing	0.726	D	0.871	deleterious	None	None	None	None	N
V/S	0.9713	likely_pathogenic	0.9714	pathogenic	-2.381	Highly Destabilizing	0.726	D	0.825	deleterious	None	None	None	None	N
V/T	0.9248	likely_pathogenic	0.9224	pathogenic	-2.051	Highly Destabilizing	0.272	N	0.724	prob.delet.	None	None	None	None	N
V/W	0.9954	likely_pathogenic	0.9951	pathogenic	-1.649	Destabilizing	0.968	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9823	likely_pathogenic	0.9818	pathogenic	-1.212	Destabilizing	0.726	D	0.746	deleterious	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.