TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35204	105835;105836;105837	chr2:178531005;178531004;178531003	chr2:179395732;179395731;179395730
N2AB	33563	100912;100913;100914	chr2:178531005;178531004;178531003	chr2:179395732;179395731;179395730
N2A	32636	98131;98132;98133	chr2:178531005;178531004;178531003	chr2:179395732;179395731;179395730
N2B	26139	78640;78641;78642	chr2:178531005;178531004;178531003	chr2:179395732;179395731;179395730
Novex-1	26264	79015;79016;79017	chr2:178531005;178531004;178531003	chr2:179395732;179395731;179395730
Novex-2	26331	79216;79217;79218	chr2:178531005;178531004;178531003	chr2:179395732;179395731;179395730
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-164
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2922
• 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	rs1474470920	-0.912	0.986	N	0.533	0.172	0.391930172978	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
E/D	rs1474470920	-0.912	0.986	N	0.533	0.172	0.391930172978	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-06	0	0
E/Q	None	None	0.999	N	0.698	0.234	0.442160178816	gnomAD-4.0.0	1.59092E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85749E-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
E/A	0.2137	likely_benign	0.2225	benign	-0.56	Destabilizing	0.972	D	0.639	neutral	D	0.523919986	None	None	N
E/C	0.8908	likely_pathogenic	0.913	pathogenic	-0.2	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/D	0.4245	ambiguous	0.42	ambiguous	-1.058	Destabilizing	0.986	D	0.533	neutral	N	0.51976496	None	None	N
E/F	0.8824	likely_pathogenic	0.8915	pathogenic	-0.707	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/G	0.2763	likely_benign	0.2891	benign	-0.849	Destabilizing	0.097	N	0.458	neutral	D	0.522978623	None	None	N
E/H	0.6	likely_pathogenic	0.6129	pathogenic	-1.031	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/I	0.626	likely_pathogenic	0.6351	pathogenic	0.197	Stabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
E/K	0.1712	likely_benign	0.2049	benign	-0.245	Destabilizing	0.986	D	0.685	prob.neutral	N	0.484014803	None	None	N
E/L	0.6544	likely_pathogenic	0.6762	pathogenic	0.197	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
E/M	0.5947	likely_pathogenic	0.6228	pathogenic	0.615	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/N	0.5005	ambiguous	0.5096	ambiguous	-0.489	Destabilizing	0.997	D	0.715	prob.delet.	None	None	None	None	N
E/P	0.9854	likely_pathogenic	0.9884	pathogenic	-0.033	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/Q	0.1371	likely_benign	0.1401	benign	-0.445	Destabilizing	0.999	D	0.698	prob.neutral	N	0.517628732	None	None	N
E/R	0.2813	likely_benign	0.3211	benign	-0.254	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/S	0.2646	likely_benign	0.2697	benign	-0.786	Destabilizing	0.979	D	0.691	prob.neutral	None	None	None	None	N
E/T	0.2781	likely_benign	0.2864	benign	-0.547	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	N
E/V	0.4062	ambiguous	0.397	ambiguous	-0.033	Destabilizing	0.999	D	0.791	deleterious	N	0.520669037	None	None	N
E/W	0.9296	likely_pathogenic	0.9442	pathogenic	-0.694	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Y	0.8229	likely_pathogenic	0.8332	pathogenic	-0.479	Destabilizing	0.999	D	0.805	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.