TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2200	6823;6824;6825	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838
N2AB	2200	6823;6824;6825	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838
N2A	2200	6823;6824;6825	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838
N2B	2154	6685;6686;6687	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838
Novex-1	2154	6685;6686;6687	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838
Novex-2	2154	6685;6686;6687	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838
Novex-3	2200	6823;6824;6825	chr2:178775113;178775112;178775111	chr2:179639840;179639839;179639838

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-11
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.388
• 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	rs1378587847	0.036	0.999	N	0.73	0.362	0.212008924253	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.63399E-04
E/K	rs1378587847	0.036	0.999	N	0.73	0.362	0.212008924253	gnomAD-4.0.0	6.84119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.93481E-04	3.59731E-06	0	3.3117E-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	0.2999	likely_benign	0.3405	ambiguous	-0.481	Destabilizing	0.999	D	0.719	prob.delet.	N	0.316855038	None	None	N
E/C	0.9603	likely_pathogenic	0.9654	pathogenic	-0.221	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/D	0.3158	likely_benign	0.3501	ambiguous	-0.466	Destabilizing	0.999	D	0.539	neutral	N	0.344208319	None	None	N
E/F	0.8897	likely_pathogenic	0.9081	pathogenic	-0.116	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/G	0.45	ambiguous	0.5006	ambiguous	-0.726	Destabilizing	1.0	D	0.691	prob.neutral	N	0.331519927	None	None	N
E/H	0.7534	likely_pathogenic	0.7924	pathogenic	0.119	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/I	0.5935	likely_pathogenic	0.6366	pathogenic	0.15	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/K	0.3649	ambiguous	0.4371	ambiguous	0.187	Stabilizing	0.999	D	0.73	prob.delet.	N	0.348620668	None	None	N
E/L	0.6131	likely_pathogenic	0.6643	pathogenic	0.15	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/M	0.6646	likely_pathogenic	0.7073	pathogenic	0.215	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/N	0.5772	likely_pathogenic	0.6263	pathogenic	-0.326	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/P	0.9543	likely_pathogenic	0.9545	pathogenic	-0.04	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/Q	0.2461	likely_benign	0.2813	benign	-0.243	Destabilizing	1.0	D	0.687	prob.neutral	N	0.34527008	None	None	N
E/R	0.5492	ambiguous	0.6152	pathogenic	0.494	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/S	0.4098	ambiguous	0.4553	ambiguous	-0.481	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
E/T	0.4997	ambiguous	0.5489	ambiguous	-0.272	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
E/V	0.3873	ambiguous	0.4235	ambiguous	-0.04	Destabilizing	1.0	D	0.751	deleterious	N	0.327970811	None	None	N
E/W	0.9793	likely_pathogenic	0.9837	pathogenic	0.113	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/Y	0.8343	likely_pathogenic	0.8635	pathogenic	0.144	Stabilizing	1.0	D	0.73	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.