TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26570	79933;79934;79935	chr2:178566424;178566423;178566422	chr2:179431151;179431150;179431149
N2AB	24929	75010;75011;75012	chr2:178566424;178566423;178566422	chr2:179431151;179431150;179431149
N2A	24002	72229;72230;72231	chr2:178566424;178566423;178566422	chr2:179431151;179431150;179431149
N2B	17505	52738;52739;52740	chr2:178566424;178566423;178566422	chr2:179431151;179431150;179431149
Novex-1	17630	53113;53114;53115	chr2:178566424;178566423;178566422	chr2:179431151;179431150;179431149
Novex-2	17697	53314;53315;53316	chr2:178566424;178566423;178566422	chr2:179431151;179431150;179431149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-81
• Domain position: 84
• Structural Position: 115
• Q(SASA): 0.1527
• 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/D	None	None	1.0	D	0.915	0.686	0.457106177737	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
G/A	0.7645	likely_pathogenic	0.7571	pathogenic	-0.596	Destabilizing	1.0	D	0.752	deleterious	D	0.550202402	None	None	I
G/C	0.8751	likely_pathogenic	0.8763	pathogenic	-0.929	Destabilizing	1.0	D	0.868	deleterious	D	0.562572666	None	None	I
G/D	0.9193	likely_pathogenic	0.9332	pathogenic	-0.759	Destabilizing	1.0	D	0.915	deleterious	D	0.542693984	None	None	I
G/E	0.9537	likely_pathogenic	0.9548	pathogenic	-0.862	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
G/F	0.983	likely_pathogenic	0.983	pathogenic	-0.998	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
G/H	0.9792	likely_pathogenic	0.9827	pathogenic	-0.961	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
G/I	0.9765	likely_pathogenic	0.9765	pathogenic	-0.424	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	I
G/K	0.9852	likely_pathogenic	0.9871	pathogenic	-1.183	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
G/L	0.9718	likely_pathogenic	0.9721	pathogenic	-0.424	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/M	0.983	likely_pathogenic	0.9824	pathogenic	-0.427	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
G/N	0.9572	likely_pathogenic	0.9654	pathogenic	-0.837	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
G/P	0.9946	likely_pathogenic	0.9963	pathogenic	-0.442	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	I
G/Q	0.9655	likely_pathogenic	0.9681	pathogenic	-1.058	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	I
G/R	0.9644	likely_pathogenic	0.9655	pathogenic	-0.764	Destabilizing	1.0	D	0.917	deleterious	D	0.561051729	None	None	I
G/S	0.6338	likely_pathogenic	0.6733	pathogenic	-1.078	Destabilizing	1.0	D	0.853	deleterious	D	0.538174534	None	None	I
G/T	0.9057	likely_pathogenic	0.9161	pathogenic	-1.102	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
G/V	0.9574	likely_pathogenic	0.9564	pathogenic	-0.442	Destabilizing	1.0	D	0.88	deleterious	D	0.528085676	None	None	I
G/W	0.9711	likely_pathogenic	0.9742	pathogenic	-1.252	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/Y	0.9703	likely_pathogenic	0.9712	pathogenic	-0.882	Destabilizing	1.0	D	0.89	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.