TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7151	21676;21677;21678	chr2:178723649;178723648;178723647	chr2:179588376;179588375;179588374
N2AB	6834	20725;20726;20727	chr2:178723649;178723648;178723647	chr2:179588376;179588375;179588374
N2A	5907	17944;17945;17946	chr2:178723649;178723648;178723647	chr2:179588376;179588375;179588374
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-56
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3064
• 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
G/V	None	None	0.978	D	0.801	0.593	0.932949919686	gnomAD-4.0.0	1.60651E-06	None	None	None	None	N	None	5.75043E-05	0	None	0	0	None	0	0	0	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
G/A	0.2977	likely_benign	0.3517	ambiguous	-0.389	Destabilizing	0.865	D	0.643	neutral	D	0.632183895	None	None	N
G/C	0.4834	ambiguous	0.5698	pathogenic	-0.838	Destabilizing	0.999	D	0.805	deleterious	D	0.658327419	None	None	N
G/D	0.2654	likely_benign	0.3064	benign	-0.84	Destabilizing	0.957	D	0.805	deleterious	D	0.586690341	None	None	N
G/E	0.2412	likely_benign	0.2794	benign	-0.997	Destabilizing	0.983	D	0.801	deleterious	None	None	None	None	N
G/F	0.7486	likely_pathogenic	0.8055	pathogenic	-1.078	Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
G/H	0.4876	ambiguous	0.5569	ambiguous	-0.74	Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
G/I	0.7234	likely_pathogenic	0.8054	pathogenic	-0.439	Destabilizing	0.992	D	0.813	deleterious	None	None	None	None	N
G/K	0.4062	ambiguous	0.4746	ambiguous	-1.017	Destabilizing	0.968	D	0.799	deleterious	None	None	None	None	N
G/L	0.6081	likely_pathogenic	0.6714	pathogenic	-0.439	Destabilizing	0.983	D	0.793	deleterious	None	None	None	None	N
G/M	0.6744	likely_pathogenic	0.7375	pathogenic	-0.39	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
G/N	0.3426	ambiguous	0.3812	ambiguous	-0.594	Destabilizing	0.345	N	0.46	neutral	None	None	None	None	N
G/P	0.955	likely_pathogenic	0.9713	pathogenic	-0.387	Destabilizing	0.992	D	0.828	deleterious	None	None	None	None	N
G/Q	0.3263	likely_benign	0.3735	ambiguous	-0.898	Destabilizing	0.983	D	0.828	deleterious	None	None	None	None	N
G/R	0.281	likely_benign	0.3384	benign	-0.531	Destabilizing	0.978	D	0.829	deleterious	D	0.632385699	None	None	N
G/S	0.1762	likely_benign	0.1968	benign	-0.725	Destabilizing	0.284	N	0.435	neutral	D	0.615962729	None	None	N
G/T	0.3901	ambiguous	0.451	ambiguous	-0.816	Destabilizing	0.968	D	0.782	deleterious	None	None	None	None	N
G/V	0.5692	likely_pathogenic	0.6664	pathogenic	-0.387	Destabilizing	0.978	D	0.801	deleterious	D	0.642106254	None	None	N
G/W	0.5514	ambiguous	0.6328	pathogenic	-1.263	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
G/Y	0.6079	likely_pathogenic	0.691	pathogenic	-0.911	Destabilizing	0.999	D	0.833	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.