TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27845	83758;83759;83760	chr2:178562599;178562598;178562597	chr2:179427326;179427325;179427324
N2AB	26204	78835;78836;78837	chr2:178562599;178562598;178562597	chr2:179427326;179427325;179427324
N2A	25277	76054;76055;76056	chr2:178562599;178562598;178562597	chr2:179427326;179427325;179427324
N2B	18780	56563;56564;56565	chr2:178562599;178562598;178562597	chr2:179427326;179427325;179427324
Novex-1	18905	56938;56939;56940	chr2:178562599;178562598;178562597	chr2:179427326;179427325;179427324
Novex-2	18972	57139;57140;57141	chr2:178562599;178562598;178562597	chr2:179427326;179427325;179427324
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: Fn3-90
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.6248
• Predicted PPI site: I

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	rs751068189	0.566	0.02	N	0.38	0.3	0.206339911435	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
E/K	rs751068189	0.566	0.02	N	0.38	0.3	0.206339911435	gnomAD-4.0.0	1.59911E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86638E-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	0.3592	ambiguous	0.3863	ambiguous	-0.455	Destabilizing	0.635	D	0.541	neutral	N	0.487310533	None	None	I
E/C	0.9622	likely_pathogenic	0.9624	pathogenic	-0.201	Destabilizing	0.997	D	0.734	prob.delet.	None	None	None	None	I
E/D	0.3203	likely_benign	0.279	benign	-0.414	Destabilizing	0.31	N	0.339	neutral	N	0.507128445	None	None	I
E/F	0.9651	likely_pathogenic	0.9678	pathogenic	-0.2	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
E/G	0.6171	likely_pathogenic	0.615	pathogenic	-0.656	Destabilizing	0.976	D	0.507	neutral	N	0.516262429	None	None	I
E/H	0.8669	likely_pathogenic	0.872	pathogenic	0.198	Stabilizing	0.994	D	0.608	neutral	None	None	None	None	I
E/I	0.5626	ambiguous	0.5777	pathogenic	0.046	Stabilizing	0.966	D	0.651	neutral	None	None	None	None	I
E/K	0.447	ambiguous	0.474	ambiguous	0.311	Stabilizing	0.02	N	0.38	neutral	N	0.50614701	None	None	I
E/L	0.7769	likely_pathogenic	0.7923	pathogenic	0.046	Stabilizing	0.933	D	0.607	neutral	None	None	None	None	I
E/M	0.762	likely_pathogenic	0.7754	pathogenic	0.064	Stabilizing	0.983	D	0.637	neutral	None	None	None	None	I
E/N	0.6339	likely_pathogenic	0.6264	pathogenic	-0.155	Destabilizing	0.867	D	0.604	neutral	None	None	None	None	I
E/P	0.8488	likely_pathogenic	0.8273	pathogenic	-0.102	Destabilizing	0.809	D	0.615	neutral	None	None	None	None	I
E/Q	0.3175	likely_benign	0.3493	ambiguous	-0.101	Destabilizing	0.822	D	0.478	neutral	N	0.469545132	None	None	I
E/R	0.6517	likely_pathogenic	0.6753	pathogenic	0.615	Stabilizing	0.937	D	0.579	neutral	None	None	None	None	I
E/S	0.5287	ambiguous	0.5335	ambiguous	-0.293	Destabilizing	0.822	D	0.527	neutral	None	None	None	None	I
E/T	0.5099	ambiguous	0.5257	ambiguous	-0.116	Destabilizing	0.957	D	0.569	neutral	None	None	None	None	I
E/V	0.4418	ambiguous	0.4638	ambiguous	-0.102	Destabilizing	0.882	D	0.601	neutral	N	0.473014626	None	None	I
E/W	0.9936	likely_pathogenic	0.9938	pathogenic	0.011	Stabilizing	0.999	D	0.741	deleterious	None	None	None	None	I
E/Y	0.9315	likely_pathogenic	0.9324	pathogenic	0.064	Stabilizing	0.998	D	0.645	neutral	None	None	None	None	I

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.