TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32282	97069;97070;97071	chr2:178543129;178543128;178543127	chr2:179407856;179407855;179407854
N2AB	30641	92146;92147;92148	chr2:178543129;178543128;178543127	chr2:179407856;179407855;179407854
N2A	29714	89365;89366;89367	chr2:178543129;178543128;178543127	chr2:179407856;179407855;179407854
N2B	23217	69874;69875;69876	chr2:178543129;178543128;178543127	chr2:179407856;179407855;179407854
Novex-1	23342	70249;70250;70251	chr2:178543129;178543128;178543127	chr2:179407856;179407855;179407854
Novex-2	23409	70450;70451;70452	chr2:178543129;178543128;178543127	chr2:179407856;179407855;179407854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-123
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.7241
• 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	rs1446694825	0.851	0.05	N	0.387	0.132	0.31291088546	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs1446694825	0.851	0.05	N	0.387	0.132	0.31291088546	gnomAD-4.0.0	3.19332E-06	None	None	None	None	I	None	0	2.28885E-05	None	0	0	None	0	0	2.87241E-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	0.1875	likely_benign	0.1563	benign	-0.282	Destabilizing	0.028	N	0.45	neutral	N	0.411081978	None	None	I
E/C	0.8656	likely_pathogenic	0.8168	pathogenic	0.228	Stabilizing	0.937	D	0.451	neutral	None	None	None	None	I
E/D	0.1816	likely_benign	0.1498	benign	-0.233	Destabilizing	None	N	0.115	neutral	N	0.417431947	None	None	I
E/F	0.8331	likely_pathogenic	0.7785	pathogenic	-0.387	Destabilizing	0.88	D	0.493	neutral	None	None	None	None	I
E/G	0.2083	likely_benign	0.1722	benign	-0.439	Destabilizing	0.16	N	0.502	neutral	N	0.4621213	None	None	I
E/H	0.4854	ambiguous	0.4331	ambiguous	-0.222	Destabilizing	0.46	N	0.331	neutral	None	None	None	None	I
E/I	0.4182	ambiguous	0.3441	ambiguous	0.084	Stabilizing	0.531	D	0.513	neutral	None	None	None	None	I
E/K	0.1805	likely_benign	0.157	benign	0.55	Stabilizing	0.05	N	0.387	neutral	N	0.429918455	None	None	I
E/L	0.4368	ambiguous	0.3699	ambiguous	0.084	Stabilizing	0.137	N	0.567	neutral	None	None	None	None	I
E/M	0.5301	ambiguous	0.4403	ambiguous	0.271	Stabilizing	0.168	N	0.479	neutral	None	None	None	None	I
E/N	0.3452	ambiguous	0.2851	benign	0.339	Stabilizing	0.069	N	0.316	neutral	None	None	None	None	I
E/P	0.4894	ambiguous	0.4435	ambiguous	-0.019	Destabilizing	0.046	N	0.485	neutral	None	None	None	None	I
E/Q	0.1317	likely_benign	0.1214	benign	0.344	Stabilizing	0.001	N	0.118	neutral	N	0.433497478	None	None	I
E/R	0.2561	likely_benign	0.234	benign	0.59	Stabilizing	0.145	N	0.331	neutral	None	None	None	None	I
E/S	0.2255	likely_benign	0.1975	benign	0.194	Stabilizing	0.003	N	0.09	neutral	None	None	None	None	I
E/T	0.2938	likely_benign	0.2477	benign	0.324	Stabilizing	0.05	N	0.438	neutral	None	None	None	None	I
E/V	0.2761	likely_benign	0.2236	benign	-0.019	Destabilizing	0.079	N	0.537	neutral	N	0.457278414	None	None	I
E/W	0.9146	likely_pathogenic	0.8743	pathogenic	-0.31	Destabilizing	0.987	D	0.481	neutral	None	None	None	None	I
E/Y	0.7019	likely_pathogenic	0.6367	pathogenic	-0.153	Destabilizing	0.866	D	0.508	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.