TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28398	85417;85418;85419	chr2:178560940;178560939;178560938	chr2:179425667;179425666;179425665
N2AB	26757	80494;80495;80496	chr2:178560940;178560939;178560938	chr2:179425667;179425666;179425665
N2A	25830	77713;77714;77715	chr2:178560940;178560939;178560938	chr2:179425667;179425666;179425665
N2B	19333	58222;58223;58224	chr2:178560940;178560939;178560938	chr2:179425667;179425666;179425665
Novex-1	19458	58597;58598;58599	chr2:178560940;178560939;178560938	chr2:179425667;179425666;179425665
Novex-2	19525	58798;58799;58800	chr2:178560940;178560939;178560938	chr2:179425667;179425666;179425665
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-143
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2176
• 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
I/V	rs878970622	None	0.437	N	0.395	0.153	None	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85798E-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
I/A	0.4456	ambiguous	0.4326	ambiguous	-2.192	Highly Destabilizing	0.919	D	0.433	neutral	None	None	None	None	I
I/C	0.8552	likely_pathogenic	0.8625	pathogenic	-1.457	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	I
I/D	0.9438	likely_pathogenic	0.9375	pathogenic	-1.803	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	I
I/E	0.8619	likely_pathogenic	0.8515	pathogenic	-1.671	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	I
I/F	0.2666	likely_benign	0.2793	benign	-1.332	Destabilizing	0.968	D	0.439	neutral	N	0.487813286	None	None	I
I/G	0.8688	likely_pathogenic	0.8586	pathogenic	-2.647	Highly Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	I
I/H	0.8859	likely_pathogenic	0.8816	pathogenic	-1.82	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	I
I/K	0.7965	likely_pathogenic	0.7847	pathogenic	-1.671	Destabilizing	0.988	D	0.707	prob.neutral	None	None	None	None	I
I/L	0.113	likely_benign	0.1196	benign	-0.937	Destabilizing	0.011	N	0.162	neutral	N	0.445704345	None	None	I
I/M	0.0953	likely_benign	0.0957	benign	-0.818	Destabilizing	0.968	D	0.457	neutral	N	0.495459835	None	None	I
I/N	0.7187	likely_pathogenic	0.7005	pathogenic	-1.708	Destabilizing	0.995	D	0.729	prob.delet.	D	0.542481672	None	None	I
I/P	0.901	likely_pathogenic	0.8917	pathogenic	-1.33	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	I
I/Q	0.8122	likely_pathogenic	0.8056	pathogenic	-1.704	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	I
I/R	0.7279	likely_pathogenic	0.713	pathogenic	-1.225	Destabilizing	0.988	D	0.729	prob.delet.	None	None	None	None	I
I/S	0.6568	likely_pathogenic	0.637	pathogenic	-2.413	Highly Destabilizing	0.984	D	0.606	neutral	D	0.530618388	None	None	I
I/T	0.2796	likely_benign	0.2704	benign	-2.137	Highly Destabilizing	0.946	D	0.496	neutral	D	0.539186309	None	None	I
I/V	0.0992	likely_benign	0.1055	benign	-1.33	Destabilizing	0.437	N	0.395	neutral	N	0.504968866	None	None	I
I/W	0.8627	likely_pathogenic	0.859	pathogenic	-1.505	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
I/Y	0.7282	likely_pathogenic	0.7365	pathogenic	-1.271	Destabilizing	0.988	D	0.562	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.