TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5275	16048;16049;16050	chr2:178733470;178733469;178733468	chr2:179598197;179598196;179598195
N2AB	4958	15097;15098;15099	chr2:178733470;178733469;178733468	chr2:179598197;179598196;179598195
N2A	4031	12316;12317;12318	chr2:178733470;178733469;178733468	chr2:179598197;179598196;179598195
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-36
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.1806
• 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
G/E	None	None	1.0	D	0.898	0.807	0.709239017261	gnomAD-4.0.0	6.84271E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99535E-07	0	0
G/R	rs1019067272	None	1.0	D	0.911	0.79	0.713845456477	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/R	rs1019067272	None	1.0	D	0.911	0.79	0.713845456477	gnomAD-4.0.0	3.09865E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.2383E-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
G/A	0.4373	ambiguous	0.4093	ambiguous	-0.289	Destabilizing	1.0	D	0.8	deleterious	D	0.794112397	None	None	I
G/C	0.7739	likely_pathogenic	0.7249	pathogenic	-0.848	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
G/D	0.7916	likely_pathogenic	0.6752	pathogenic	-0.635	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	I
G/E	0.815	likely_pathogenic	0.6876	pathogenic	-0.809	Destabilizing	1.0	D	0.898	deleterious	D	0.731395526	None	None	I
G/F	0.9471	likely_pathogenic	0.9162	pathogenic	-1.106	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
G/H	0.872	likely_pathogenic	0.8	pathogenic	-0.516	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/I	0.9497	likely_pathogenic	0.9155	pathogenic	-0.493	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
G/K	0.8441	likely_pathogenic	0.7293	pathogenic	-0.706	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	I
G/L	0.8681	likely_pathogenic	0.8232	pathogenic	-0.493	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/M	0.8932	likely_pathogenic	0.8447	pathogenic	-0.416	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/N	0.7012	likely_pathogenic	0.6106	pathogenic	-0.389	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
G/P	0.9953	likely_pathogenic	0.9935	pathogenic	-0.394	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
G/Q	0.7563	likely_pathogenic	0.6514	pathogenic	-0.715	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	I
G/R	0.7081	likely_pathogenic	0.5859	pathogenic	-0.247	Destabilizing	1.0	D	0.911	deleterious	D	0.671290786	None	None	I
G/S	0.2848	likely_benign	0.2468	benign	-0.509	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/T	0.6665	likely_pathogenic	0.5558	ambiguous	-0.622	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
G/V	0.8809	likely_pathogenic	0.8278	pathogenic	-0.394	Destabilizing	1.0	D	0.872	deleterious	D	0.826823217	None	None	I
G/W	0.8934	likely_pathogenic	0.8367	pathogenic	-1.229	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/Y	0.9188	likely_pathogenic	0.8809	pathogenic	-0.882	Destabilizing	1.0	D	0.874	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.