TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32086	96481;96482;96483	chr2:178543888;178543887;178543886	chr2:179408615;179408614;179408613
N2AB	30445	91558;91559;91560	chr2:178543888;178543887;178543886	chr2:179408615;179408614;179408613
N2A	29518	88777;88778;88779	chr2:178543888;178543887;178543886	chr2:179408615;179408614;179408613
N2B	23021	69286;69287;69288	chr2:178543888;178543887;178543886	chr2:179408615;179408614;179408613
Novex-1	23146	69661;69662;69663	chr2:178543888;178543887;178543886	chr2:179408615;179408614;179408613
Novex-2	23213	69862;69863;69864	chr2:178543888;178543887;178543886	chr2:179408615;179408614;179408613
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-153
• Domain position: 70
• Structural Position: 157
• Q(SASA): 0.3258
• 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	rs775945524	-0.264	0.999	N	0.669	0.442	0.406945738958	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs775945524	-0.264	0.999	N	0.669	0.442	0.406945738958	gnomAD-4.0.0	3.18303E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	0	None	0	0	2.85886E-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	0.1457	likely_benign	0.1423	benign	-0.78	Destabilizing	0.999	D	0.729	prob.delet.	N	0.508046456	None	None	N
E/C	0.7276	likely_pathogenic	0.7142	pathogenic	-0.282	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
E/D	0.2518	likely_benign	0.2404	benign	-0.999	Destabilizing	0.999	D	0.599	neutral	N	0.521226397	None	None	N
E/F	0.6602	likely_pathogenic	0.6287	pathogenic	-0.821	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
E/G	0.2856	likely_benign	0.2611	benign	-1.071	Destabilizing	1.0	D	0.812	deleterious	N	0.489366541	None	None	N
E/H	0.3708	ambiguous	0.3537	ambiguous	-1.146	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/I	0.2328	likely_benign	0.2232	benign	-0.012	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
E/K	0.1641	likely_benign	0.1459	benign	-0.302	Destabilizing	0.999	D	0.669	neutral	N	0.434220701	None	None	N
E/L	0.3156	likely_benign	0.2958	benign	-0.012	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
E/M	0.3285	likely_benign	0.3084	benign	0.456	Stabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
E/N	0.3045	likely_benign	0.29	benign	-0.568	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/P	0.9915	likely_pathogenic	0.9878	pathogenic	-0.247	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
E/Q	0.1194	likely_benign	0.1177	benign	-0.522	Destabilizing	1.0	D	0.699	prob.neutral	N	0.463119456	None	None	N
E/R	0.2601	likely_benign	0.2331	benign	-0.295	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/S	0.1856	likely_benign	0.1801	benign	-0.872	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/T	0.1281	likely_benign	0.1321	benign	-0.627	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
E/V	0.1408	likely_benign	0.1393	benign	-0.247	Destabilizing	1.0	D	0.87	deleterious	N	0.388488412	None	None	N
E/W	0.8715	likely_pathogenic	0.8446	pathogenic	-0.727	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/Y	0.578	likely_pathogenic	0.5526	ambiguous	-0.579	Destabilizing	1.0	D	0.89	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.