TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23949	72070;72071;72072	chr2:178574287;178574286;178574285	chr2:179439014;179439013;179439012
N2AB	22308	67147;67148;67149	chr2:178574287;178574286;178574285	chr2:179439014;179439013;179439012
N2A	21381	64366;64367;64368	chr2:178574287;178574286;178574285	chr2:179439014;179439013;179439012
N2B	14884	44875;44876;44877	chr2:178574287;178574286;178574285	chr2:179439014;179439013;179439012
Novex-1	15009	45250;45251;45252	chr2:178574287;178574286;178574285	chr2:179439014;179439013;179439012
Novex-2	15076	45451;45452;45453	chr2:178574287;178574286;178574285	chr2:179439014;179439013;179439012
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: Fn3-62
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.9655
• 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	rs866868965	0.55	0.958	N	0.641	0.387	0.290962096972	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
E/K	rs866868965	0.55	0.958	N	0.641	0.387	0.290962096972	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs866868965	0.55	0.958	N	0.641	0.387	0.290962096972	gnomAD-4.0.0	3.09957E-06	None	None	None	None	N	None	4.00641E-05	0	None	0	0	None	0	0	8.47794E-07	0	1.60149E-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	0.1013	likely_benign	0.1046	benign	-0.338	Destabilizing	0.067	N	0.355	neutral	N	0.464108386	None	None	N
E/C	0.776	likely_pathogenic	0.7752	pathogenic	-0.257	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.1427	likely_benign	0.1493	benign	-0.398	Destabilizing	0.979	D	0.581	neutral	N	0.497663599	None	None	N
E/F	0.6481	likely_pathogenic	0.6744	pathogenic	-0.168	Destabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	N
E/G	0.1363	likely_benign	0.1479	benign	-0.534	Destabilizing	0.919	D	0.558	neutral	N	0.482542218	None	None	N
E/H	0.3735	ambiguous	0.3791	ambiguous	0.203	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.2341	likely_benign	0.2332	benign	0.142	Stabilizing	0.991	D	0.69	prob.neutral	None	None	None	None	N
E/K	0.1053	likely_benign	0.109	benign	0.162	Stabilizing	0.958	D	0.641	neutral	N	0.457219699	None	None	N
E/L	0.2689	likely_benign	0.274	benign	0.142	Stabilizing	0.982	D	0.604	neutral	None	None	None	None	N
E/M	0.3501	ambiguous	0.3504	ambiguous	0.064	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
E/N	0.1988	likely_benign	0.2072	benign	-0.164	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
E/P	0.4643	ambiguous	0.4611	ambiguous	0.002	Stabilizing	0.995	D	0.664	neutral	None	None	None	None	N
E/Q	0.1068	likely_benign	0.1065	benign	-0.122	Destabilizing	0.994	D	0.623	neutral	N	0.472325225	None	None	N
E/R	0.1732	likely_benign	0.1768	benign	0.476	Stabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
E/S	0.1483	likely_benign	0.1558	benign	-0.327	Destabilizing	0.938	D	0.636	neutral	None	None	None	None	N
E/T	0.1646	likely_benign	0.1681	benign	-0.169	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	N
E/V	0.1481	likely_benign	0.1477	benign	0.002	Stabilizing	0.976	D	0.54	neutral	N	0.491527061	None	None	N
E/W	0.8504	likely_pathogenic	0.8642	pathogenic	-0.023	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/Y	0.5268	ambiguous	0.5434	ambiguous	0.066	Stabilizing	0.998	D	0.661	neutral	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.