TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29076	87451;87452;87453	chr2:178558128;178558127;178558126	chr2:179422855;179422854;179422853
N2AB	27435	82528;82529;82530	chr2:178558128;178558127;178558126	chr2:179422855;179422854;179422853
N2A	26508	79747;79748;79749	chr2:178558128;178558127;178558126	chr2:179422855;179422854;179422853
N2B	20011	60256;60257;60258	chr2:178558128;178558127;178558126	chr2:179422855;179422854;179422853
Novex-1	20136	60631;60632;60633	chr2:178558128;178558127;178558126	chr2:179422855;179422854;179422853
Novex-2	20203	60832;60833;60834	chr2:178558128;178558127;178558126	chr2:179422855;179422854;179422853
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-145
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2877
• 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
V/A	None	None	0.999	D	0.676	0.713	0.737052393128	gnomAD-4.0.0	2.05256E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	5.20472E-04	0	0	0
V/L	rs776219010	-0.313	0.997	D	0.704	0.473	0.678378258981	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	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
V/A	0.3603	ambiguous	0.3381	benign	-1.415	Destabilizing	0.999	D	0.676	prob.neutral	D	0.536242762	None	None	I
V/C	0.79	likely_pathogenic	0.7648	pathogenic	-1.074	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
V/D	0.9672	likely_pathogenic	0.9487	pathogenic	-1.129	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
V/E	0.9322	likely_pathogenic	0.8999	pathogenic	-1.088	Destabilizing	1.0	D	0.867	deleterious	D	0.574630292	None	None	I
V/F	0.3382	likely_benign	0.2637	benign	-0.967	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
V/G	0.625	likely_pathogenic	0.5746	pathogenic	-1.772	Destabilizing	1.0	D	0.859	deleterious	D	0.574630292	None	None	I
V/H	0.9561	likely_pathogenic	0.9368	pathogenic	-1.272	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
V/I	0.079	likely_benign	0.0776	benign	-0.524	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	I
V/K	0.9397	likely_pathogenic	0.915	pathogenic	-1.269	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
V/L	0.2666	likely_benign	0.2293	benign	-0.524	Destabilizing	0.997	D	0.704	prob.neutral	D	0.53973595	None	None	I
V/M	0.2396	likely_benign	0.1936	benign	-0.522	Destabilizing	1.0	D	0.753	deleterious	D	0.557975158	None	None	I
V/N	0.884	likely_pathogenic	0.8507	pathogenic	-1.115	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/P	0.8215	likely_pathogenic	0.8066	pathogenic	-0.786	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
V/Q	0.9212	likely_pathogenic	0.8848	pathogenic	-1.186	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
V/R	0.9285	likely_pathogenic	0.8959	pathogenic	-0.845	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
V/S	0.7203	likely_pathogenic	0.671	pathogenic	-1.671	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	I
V/T	0.5037	ambiguous	0.4841	ambiguous	-1.5	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
V/W	0.9404	likely_pathogenic	0.9072	pathogenic	-1.174	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
V/Y	0.8007	likely_pathogenic	0.7296	pathogenic	-0.875	Destabilizing	1.0	D	0.791	deleterious	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.