TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14340	43243;43244;43245	chr2:178633255;178633254;178633253	chr2:179497982;179497981;179497980
N2AB	12699	38320;38321;38322	chr2:178633255;178633254;178633253	chr2:179497982;179497981;179497980
N2A	11772	35539;35540;35541	chr2:178633255;178633254;178633253	chr2:179497982;179497981;179497980
N2B	5275	16048;16049;16050	chr2:178633255;178633254;178633253	chr2:179497982;179497981;179497980
Novex-1	5400	16423;16424;16425	chr2:178633255;178633254;178633253	chr2:179497982;179497981;179497980
Novex-2	5467	16624;16625;16626	chr2:178633255;178633254;178633253	chr2:179497982;179497981;179497980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-94
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0735
• 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
I/T	rs397517571	-3.424	0.682	N	0.837	0.354	0.333651784274	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.9E-06	1.66389E-04
I/T	rs397517571	-3.424	0.682	N	0.837	0.354	0.333651784274	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	3.92979E-04	0	2.88351E-04	0	None	0	0	0	0	0
I/T	rs397517571	-3.424	0.682	N	0.837	0.354	0.333651784274	gnomAD-4.0.0	1.36363E-05	None	None	None	None	N	None	2.66681E-05	1.0001E-04	None	3.37998E-05	0	None	0	0	5.08681E-06	0	1.12086E-04

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
I/A	0.5802	likely_pathogenic	0.5878	pathogenic	-3.182	Highly Destabilizing	0.37	N	0.758	deleterious	None	None	None	None	N
I/C	0.8716	likely_pathogenic	0.8447	pathogenic	-2.286	Highly Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
I/D	0.9951	likely_pathogenic	0.9957	pathogenic	-3.779	Highly Destabilizing	0.984	D	0.901	deleterious	None	None	None	None	N
I/E	0.9831	likely_pathogenic	0.9863	pathogenic	-3.48	Highly Destabilizing	0.953	D	0.862	deleterious	None	None	None	None	N
I/F	0.6506	likely_pathogenic	0.7443	pathogenic	-1.853	Destabilizing	0.883	D	0.729	deleterious	N	0.420734262	None	None	N
I/G	0.9503	likely_pathogenic	0.9493	pathogenic	-3.738	Highly Destabilizing	0.953	D	0.798	deleterious	None	None	None	None	N
I/H	0.9915	likely_pathogenic	0.9936	pathogenic	-3.218	Highly Destabilizing	0.996	D	0.862	deleterious	None	None	None	None	N
I/K	0.979	likely_pathogenic	0.9842	pathogenic	-2.528	Highly Destabilizing	0.953	D	0.865	deleterious	None	None	None	None	N
I/L	0.2742	likely_benign	0.2452	benign	-1.492	Destabilizing	0.162	N	0.386	neutral	N	0.433832381	None	None	N
I/M	0.1662	likely_benign	0.1874	benign	-1.63	Destabilizing	0.938	D	0.719	prob.delet.	N	0.421375605	None	None	N
I/N	0.9316	likely_pathogenic	0.9406	pathogenic	-3.153	Highly Destabilizing	0.979	D	0.894	deleterious	N	0.421655193	None	None	N
I/P	0.9916	likely_pathogenic	0.9927	pathogenic	-2.05	Highly Destabilizing	0.984	D	0.899	deleterious	None	None	None	None	N
I/Q	0.9785	likely_pathogenic	0.9823	pathogenic	-2.865	Highly Destabilizing	0.984	D	0.892	deleterious	None	None	None	None	N
I/R	0.9643	likely_pathogenic	0.9736	pathogenic	-2.376	Highly Destabilizing	0.953	D	0.891	deleterious	None	None	None	None	N
I/S	0.8451	likely_pathogenic	0.8624	pathogenic	-3.693	Highly Destabilizing	0.938	D	0.795	deleterious	N	0.421375605	None	None	N
I/T	0.381	ambiguous	0.4866	ambiguous	-3.256	Highly Destabilizing	0.682	D	0.837	deleterious	N	0.404487185	None	None	N
I/V	0.1122	likely_benign	0.1013	benign	-2.05	Highly Destabilizing	0.001	N	0.201	neutral	N	0.36176044	None	None	N
I/W	0.9903	likely_pathogenic	0.9925	pathogenic	-2.234	Highly Destabilizing	0.996	D	0.86	deleterious	None	None	None	None	N
I/Y	0.9637	likely_pathogenic	0.9733	pathogenic	-2.121	Highly Destabilizing	0.953	D	0.856	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.