TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27749	83470;83471;83472	chr2:178562887;178562886;178562885	chr2:179427614;179427613;179427612
N2AB	26108	78547;78548;78549	chr2:178562887;178562886;178562885	chr2:179427614;179427613;179427612
N2A	25181	75766;75767;75768	chr2:178562887;178562886;178562885	chr2:179427614;179427613;179427612
N2B	18684	56275;56276;56277	chr2:178562887;178562886;178562885	chr2:179427614;179427613;179427612
Novex-1	18809	56650;56651;56652	chr2:178562887;178562886;178562885	chr2:179427614;179427613;179427612
Novex-2	18876	56851;56852;56853	chr2:178562887;178562886;178562885	chr2:179427614;179427613;179427612
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-141
• Domain position: 74
• Structural Position: 159
• Q(SASA): 0.4496
• 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/G	None	None	0.822	N	0.68	0.506	0.522770035047	gnomAD-4.0.0	1.59228E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-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	0.2168	likely_benign	0.2071	benign	-0.452	Destabilizing	0.698	D	0.593	neutral	N	0.498405442	None	None	N
E/C	0.8223	likely_pathogenic	0.8119	pathogenic	0.23	Stabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
E/D	0.3913	ambiguous	0.3911	ambiguous	-0.459	Destabilizing	0.014	N	0.324	neutral	N	0.513244467	None	None	N
E/F	0.8569	likely_pathogenic	0.8393	pathogenic	-0.682	Destabilizing	0.956	D	0.792	deleterious	None	None	None	None	N
E/G	0.3478	ambiguous	0.3302	benign	-0.646	Destabilizing	0.822	D	0.68	prob.neutral	N	0.514004936	None	None	N
E/H	0.5104	ambiguous	0.5	ambiguous	-0.839	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
E/I	0.3504	ambiguous	0.3376	benign	0.026	Stabilizing	0.915	D	0.718	prob.delet.	None	None	None	None	N
E/K	0.1913	likely_benign	0.1685	benign	0.385	Stabilizing	0.822	D	0.631	neutral	N	0.506371588	None	None	N
E/L	0.5112	ambiguous	0.4949	ambiguous	0.026	Stabilizing	0.754	D	0.705	prob.neutral	None	None	None	None	N
E/M	0.4865	ambiguous	0.4719	ambiguous	0.427	Stabilizing	0.994	D	0.769	deleterious	None	None	None	None	N
E/N	0.4494	ambiguous	0.4298	ambiguous	0.174	Stabilizing	0.915	D	0.645	neutral	None	None	None	None	N
E/P	0.9884	likely_pathogenic	0.9902	pathogenic	-0.114	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
E/Q	0.1009	likely_benign	0.097	benign	0.172	Stabilizing	0.942	D	0.633	neutral	N	0.487138042	None	None	N
E/R	0.308	likely_benign	0.2848	benign	0.296	Stabilizing	0.978	D	0.668	neutral	None	None	None	None	N
E/S	0.2706	likely_benign	0.2561	benign	0.007	Stabilizing	0.86	D	0.623	neutral	None	None	None	None	N
E/T	0.2071	likely_benign	0.1915	benign	0.168	Stabilizing	0.86	D	0.642	neutral	None	None	None	None	N
E/V	0.1905	likely_benign	0.1856	benign	-0.114	Destabilizing	0.032	N	0.492	neutral	N	0.492417961	None	None	N
E/W	0.9437	likely_pathogenic	0.9398	pathogenic	-0.627	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
E/Y	0.7952	likely_pathogenic	0.7802	pathogenic	-0.449	Destabilizing	0.978	D	0.779	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.