TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1088	3487;3488;3489	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055
N2AB	1088	3487;3488;3489	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055
N2A	1088	3487;3488;3489	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055
N2B	1042	3349;3350;3351	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055
Novex-1	1042	3349;3350;3351	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055
Novex-2	1042	3349;3350;3351	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055
Novex-3	1088	3487;3488;3489	chr2:178782330;178782329;178782328	chr2:179647057;179647056;179647055

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-4
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1803
• Predicted PPI site: I

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
P/S	None	None	1.0	D	0.851	0.523	0.293147016451	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
P/A	0.6204	likely_pathogenic	0.5655	pathogenic	-1.411	Destabilizing	1.0	D	0.785	deleterious	D	0.560124779	None	None	I
P/C	0.9887	likely_pathogenic	0.9827	pathogenic	-0.989	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
P/D	0.9931	likely_pathogenic	0.9896	pathogenic	-0.845	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
P/E	0.9824	likely_pathogenic	0.9758	pathogenic	-0.705	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/F	0.9943	likely_pathogenic	0.9915	pathogenic	-0.772	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/G	0.9644	likely_pathogenic	0.9514	pathogenic	-1.869	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/H	0.9863	likely_pathogenic	0.9792	pathogenic	-1.406	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/I	0.9309	likely_pathogenic	0.9057	pathogenic	-0.196	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
P/K	0.9933	likely_pathogenic	0.9899	pathogenic	-0.939	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
P/L	0.6585	likely_pathogenic	0.6043	pathogenic	-0.196	Destabilizing	1.0	D	0.901	deleterious	N	0.447263924	None	None	I
P/M	0.9396	likely_pathogenic	0.9189	pathogenic	-0.289	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/N	0.988	likely_pathogenic	0.9812	pathogenic	-0.999	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	I
P/Q	0.976	likely_pathogenic	0.9668	pathogenic	-0.907	Destabilizing	1.0	D	0.883	deleterious	D	0.625754834	None	None	I
P/R	0.9841	likely_pathogenic	0.9769	pathogenic	-0.805	Destabilizing	1.0	D	0.901	deleterious	D	0.602611244	None	None	I
P/S	0.9445	likely_pathogenic	0.9198	pathogenic	-1.716	Destabilizing	1.0	D	0.851	deleterious	D	0.544237245	None	None	I
P/T	0.8612	likely_pathogenic	0.8185	pathogenic	-1.422	Destabilizing	1.0	D	0.861	deleterious	N	0.494974506	None	None	I
P/V	0.8504	likely_pathogenic	0.7937	pathogenic	-0.567	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
P/W	0.9986	likely_pathogenic	0.9978	pathogenic	-1.071	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
P/Y	0.996	likely_pathogenic	0.9934	pathogenic	-0.685	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I

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.