TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17076	51451;51452;51453	chr2:178610300;178610299;178610298	chr2:179475027;179475026;179475025
N2AB	15435	46528;46529;46530	chr2:178610300;178610299;178610298	chr2:179475027;179475026;179475025
N2A	14508	43747;43748;43749	chr2:178610300;178610299;178610298	chr2:179475027;179475026;179475025
N2B	8011	24256;24257;24258	chr2:178610300;178610299;178610298	chr2:179475027;179475026;179475025
Novex-1	8136	24631;24632;24633	chr2:178610300;178610299;178610298	chr2:179475027;179475026;179475025
Novex-2	8203	24832;24833;24834	chr2:178610300;178610299;178610298	chr2:179475027;179475026;179475025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-12
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5032
• 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
G/E	None	None	0.999	D	0.79	0.437	0.478905595755	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
G/A	0.7667	likely_pathogenic	0.7458	pathogenic	-0.288	Destabilizing	0.995	D	0.601	neutral	D	0.629273471	None	None	I
G/C	0.867	likely_pathogenic	0.849	pathogenic	-0.933	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/D	0.8464	likely_pathogenic	0.7915	pathogenic	-0.47	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	I
G/E	0.9123	likely_pathogenic	0.8866	pathogenic	-0.625	Destabilizing	0.999	D	0.79	deleterious	D	0.631934822	None	None	I
G/F	0.9774	likely_pathogenic	0.9698	pathogenic	-0.959	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/H	0.9571	likely_pathogenic	0.9387	pathogenic	-0.412	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
G/I	0.9734	likely_pathogenic	0.9675	pathogenic	-0.441	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/K	0.9678	likely_pathogenic	0.9547	pathogenic	-0.78	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
G/L	0.9563	likely_pathogenic	0.9422	pathogenic	-0.441	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
G/M	0.9661	likely_pathogenic	0.9567	pathogenic	-0.569	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/N	0.8329	likely_pathogenic	0.798	pathogenic	-0.473	Destabilizing	0.669	D	0.627	neutral	None	None	None	None	I
G/P	0.9976	likely_pathogenic	0.9964	pathogenic	-0.358	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/Q	0.92	likely_pathogenic	0.8974	pathogenic	-0.733	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/R	0.9307	likely_pathogenic	0.9062	pathogenic	-0.33	Destabilizing	0.999	D	0.801	deleterious	D	0.631266705	None	None	I
G/S	0.54	ambiguous	0.5083	ambiguous	-0.639	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
G/T	0.9148	likely_pathogenic	0.8923	pathogenic	-0.72	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	I
G/V	0.9574	likely_pathogenic	0.9495	pathogenic	-0.358	Destabilizing	0.999	D	0.801	deleterious	D	0.724935215	None	None	I
G/W	0.9748	likely_pathogenic	0.9611	pathogenic	-1.098	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/Y	0.967	likely_pathogenic	0.9533	pathogenic	-0.765	Destabilizing	1.0	D	0.815	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.