TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15234	45925;45926;45927	chr2:178620910;178620909;178620908	chr2:179485637;179485636;179485635
N2AB	13593	41002;41003;41004	chr2:178620910;178620909;178620908	chr2:179485637;179485636;179485635
N2A	12666	38221;38222;38223	chr2:178620910;178620909;178620908	chr2:179485637;179485636;179485635
N2B	6169	18730;18731;18732	chr2:178620910;178620909;178620908	chr2:179485637;179485636;179485635
Novex-1	6294	19105;19106;19107	chr2:178620910;178620909;178620908	chr2:179485637;179485636;179485635
Novex-2	6361	19306;19307;19308	chr2:178620910;178620909;178620908	chr2:179485637;179485636;179485635
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: Ig-104
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5833
• 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/K	rs1457956988	None	0.822	N	0.623	0.353	0.396645960531	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	1.94856E-04	None	0	0	0	2.06954E-04	0
E/K	rs1457956988	None	0.822	N	0.623	0.353	0.396645960531	gnomAD-4.0.0	7.69807E-06	None	None	None	None	N	None	0	0	None	0	9.74991E-05	None	0	0	0	1.34081E-05	2.849E-05

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	0.2218	likely_benign	0.1713	benign	-0.055	Destabilizing	0.822	D	0.649	neutral	N	0.508628001	None	None	N
E/C	0.9661	likely_pathogenic	0.9389	pathogenic	-0.049	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
E/D	0.2365	likely_benign	0.168	benign	-0.288	Destabilizing	0.006	N	0.268	neutral	N	0.504722144	None	None	N
E/F	0.9274	likely_pathogenic	0.8724	pathogenic	-0.015	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.336	likely_benign	0.2341	benign	-0.203	Destabilizing	0.822	D	0.63	neutral	N	0.512907873	None	None	N
E/H	0.7698	likely_pathogenic	0.6772	pathogenic	0.474	Stabilizing	0.998	D	0.663	neutral	None	None	None	None	N
E/I	0.6326	likely_pathogenic	0.5095	ambiguous	0.283	Stabilizing	0.978	D	0.75	deleterious	None	None	None	None	N
E/K	0.2445	likely_benign	0.1971	benign	0.553	Stabilizing	0.822	D	0.623	neutral	N	0.509516008	None	None	N
E/L	0.6953	likely_pathogenic	0.5573	ambiguous	0.283	Stabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	N
E/M	0.752	likely_pathogenic	0.6421	pathogenic	0.134	Stabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
E/N	0.5312	ambiguous	0.3862	ambiguous	0.215	Stabilizing	0.915	D	0.641	neutral	None	None	None	None	N
E/P	0.5823	likely_pathogenic	0.4917	ambiguous	0.19	Stabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	N
E/Q	0.2699	likely_benign	0.2186	benign	0.24	Stabilizing	0.942	D	0.615	neutral	D	0.545860394	None	None	N
E/R	0.4297	ambiguous	0.3673	ambiguous	0.763	Stabilizing	0.978	D	0.686	prob.neutral	None	None	None	None	N
E/S	0.3549	ambiguous	0.2618	benign	0.097	Stabilizing	0.86	D	0.629	neutral	None	None	None	None	N
E/T	0.4157	ambiguous	0.3055	benign	0.226	Stabilizing	0.956	D	0.619	neutral	None	None	None	None	N
E/V	0.3948	ambiguous	0.2989	benign	0.19	Stabilizing	0.971	D	0.716	prob.delet.	N	0.509043974	None	None	N
E/W	0.9725	likely_pathogenic	0.955	pathogenic	0.069	Stabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
E/Y	0.8722	likely_pathogenic	0.7998	pathogenic	0.226	Stabilizing	0.998	D	0.727	prob.delet.	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.