TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16829	50710;50711;50712	chr2:178611824;178611823;178611822	chr2:179476551;179476550;179476549
N2AB	15188	45787;45788;45789	chr2:178611824;178611823;178611822	chr2:179476551;179476550;179476549
N2A	14261	43006;43007;43008	chr2:178611824;178611823;178611822	chr2:179476551;179476550;179476549
N2B	7764	23515;23516;23517	chr2:178611824;178611823;178611822	chr2:179476551;179476550;179476549
Novex-1	7889	23890;23891;23892	chr2:178611824;178611823;178611822	chr2:179476551;179476550;179476549
Novex-2	7956	24091;24092;24093	chr2:178611824;178611823;178611822	chr2:179476551;179476550;179476549
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-10
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.264
• 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
E/D	rs777736610	-1.696	0.834	D	0.387	0.239	0.349647731962	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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
E/A	0.7266	likely_pathogenic	0.6289	pathogenic	-1.023	Destabilizing	0.716	D	0.493	neutral	N	0.491314575	None	None	N
E/C	0.9846	likely_pathogenic	0.9777	pathogenic	-0.773	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
E/D	0.8718	likely_pathogenic	0.8379	pathogenic	-1.597	Destabilizing	0.834	D	0.387	neutral	D	0.614839725	None	None	N
E/F	0.9845	likely_pathogenic	0.9768	pathogenic	-1.001	Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
E/G	0.8659	likely_pathogenic	0.8047	pathogenic	-1.39	Destabilizing	0.946	D	0.711	prob.delet.	D	0.614839725	None	None	N
E/H	0.9736	likely_pathogenic	0.9576	pathogenic	-1.266	Destabilizing	0.994	D	0.653	neutral	None	None	None	None	N
E/I	0.8365	likely_pathogenic	0.7916	pathogenic	-0.016	Destabilizing	0.979	D	0.843	deleterious	None	None	None	None	N
E/K	0.8306	likely_pathogenic	0.7598	pathogenic	-1.11	Destabilizing	0.016	N	0.295	neutral	N	0.467929891	None	None	N
E/L	0.9417	likely_pathogenic	0.9082	pathogenic	-0.016	Destabilizing	0.959	D	0.793	deleterious	None	None	None	None	N
E/M	0.8991	likely_pathogenic	0.8544	pathogenic	0.53	Stabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
E/N	0.9595	likely_pathogenic	0.9411	pathogenic	-1.383	Destabilizing	0.959	D	0.621	neutral	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.999	pathogenic	-0.332	Destabilizing	0.979	D	0.793	deleterious	None	None	None	None	N
E/Q	0.4984	ambiguous	0.4172	ambiguous	-1.212	Destabilizing	0.716	D	0.533	neutral	N	0.469100983	None	None	N
E/R	0.9059	likely_pathogenic	0.8626	pathogenic	-1.021	Destabilizing	0.921	D	0.617	neutral	None	None	None	None	N
E/S	0.8208	likely_pathogenic	0.7512	pathogenic	-1.873	Destabilizing	0.769	D	0.42	neutral	None	None	None	None	N
E/T	0.8623	likely_pathogenic	0.8054	pathogenic	-1.546	Destabilizing	0.959	D	0.711	prob.delet.	None	None	None	None	N
E/V	0.6656	likely_pathogenic	0.5913	pathogenic	-0.332	Destabilizing	0.946	D	0.777	deleterious	N	0.454885652	None	None	N
E/W	0.996	likely_pathogenic	0.9936	pathogenic	-1.049	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
E/Y	0.9843	likely_pathogenic	0.9761	pathogenic	-0.803	Destabilizing	0.993	D	0.825	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.