TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35499	106720;106721;106722	chr2:178529996;178529995;178529994	chr2:179394723;179394722;179394721
N2AB	33858	101797;101798;101799	chr2:178529996;178529995;178529994	chr2:179394723;179394722;179394721
N2A	32931	99016;99017;99018	chr2:178529996;178529995;178529994	chr2:179394723;179394722;179394721
N2B	26434	79525;79526;79527	chr2:178529996;178529995;178529994	chr2:179394723;179394722;179394721
Novex-1	26559	79900;79901;79902	chr2:178529996;178529995;178529994	chr2:179394723;179394722;179394721
Novex-2	26626	80101;80102;80103	chr2:178529996;178529995;178529994	chr2:179394723;179394722;179394721
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-166
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.159
• 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	rs1211721189	None	0.997	D	0.747	0.727	0.731043292528	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
G/R	rs779794234	None	0.747	D	0.449	0.635	0.707253505956	gnomAD-4.0.0	1.62014E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87887E-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	0.4261	ambiguous	0.4458	ambiguous	-0.287	Destabilizing	0.995	D	0.547	neutral	D	0.592014076	None	None	I
G/C	0.7729	likely_pathogenic	0.7806	pathogenic	-0.915	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
G/D	0.6683	likely_pathogenic	0.6794	pathogenic	-0.534	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
G/E	0.7101	likely_pathogenic	0.7284	pathogenic	-0.704	Destabilizing	0.997	D	0.747	deleterious	D	0.533828527	None	None	I
G/F	0.9225	likely_pathogenic	0.9222	pathogenic	-1.05	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/H	0.9088	likely_pathogenic	0.9104	pathogenic	-0.457	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/I	0.8778	likely_pathogenic	0.8819	pathogenic	-0.494	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/K	0.9074	likely_pathogenic	0.9095	pathogenic	-0.731	Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	I
G/L	0.8995	likely_pathogenic	0.9052	pathogenic	-0.494	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	I
G/M	0.9311	likely_pathogenic	0.9357	pathogenic	-0.515	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
G/N	0.7689	likely_pathogenic	0.7701	pathogenic	-0.42	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
G/P	0.9908	likely_pathogenic	0.9912	pathogenic	-0.394	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
G/Q	0.829	likely_pathogenic	0.835	pathogenic	-0.715	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
G/R	0.8098	likely_pathogenic	0.8155	pathogenic	-0.281	Destabilizing	0.747	D	0.449	neutral	D	0.617753992	None	None	I
G/S	0.301	likely_benign	0.3085	benign	-0.561	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
G/T	0.6928	likely_pathogenic	0.6934	pathogenic	-0.663	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	I
G/V	0.771	likely_pathogenic	0.7842	pathogenic	-0.394	Destabilizing	0.999	D	0.746	deleterious	D	0.634378765	None	None	I
G/W	0.9072	likely_pathogenic	0.9063	pathogenic	-1.17	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
G/Y	0.8841	likely_pathogenic	0.8837	pathogenic	-0.835	Destabilizing	1.0	D	0.779	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.