TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8167	24724;24725;24726	chr2:178718701;178718700;178718699	chr2:179583428;179583427;179583426
N2AB	7850	23773;23774;23775	chr2:178718701;178718700;178718699	chr2:179583428;179583427;179583426
N2A	6923	20992;20993;20994	chr2:178718701;178718700;178718699	chr2:179583428;179583427;179583426
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-66
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.2963
• 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
V/M	None	None	0.999	D	0.843	0.601	0.734339438395	gnomAD-4.0.0	1.593E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86172E-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
V/A	0.8015	likely_pathogenic	0.8224	pathogenic	-2.044	Highly Destabilizing	0.998	D	0.693	prob.neutral	D	0.634073367	None	None	N
V/C	0.9589	likely_pathogenic	0.9502	pathogenic	-1.517	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/D	0.9952	likely_pathogenic	0.9948	pathogenic	-2.652	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/E	0.979	likely_pathogenic	0.9758	pathogenic	-2.451	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.63467878	None	None	N
V/F	0.844	likely_pathogenic	0.8563	pathogenic	-1.194	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/G	0.9069	likely_pathogenic	0.9059	pathogenic	-2.539	Highly Destabilizing	1.0	D	0.781	deleterious	D	0.63467878	None	None	N
V/H	0.9935	likely_pathogenic	0.9926	pathogenic	-2.28	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/I	0.0995	likely_benign	0.1124	benign	-0.669	Destabilizing	0.813	D	0.549	neutral	None	None	None	None	N
V/K	0.985	likely_pathogenic	0.9806	pathogenic	-1.664	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/L	0.6136	likely_pathogenic	0.6356	pathogenic	-0.669	Destabilizing	0.981	D	0.705	prob.neutral	D	0.578657454	None	None	N
V/M	0.6789	likely_pathogenic	0.702	pathogenic	-0.771	Destabilizing	0.999	D	0.843	deleterious	D	0.634275171	None	None	N
V/N	0.9821	likely_pathogenic	0.982	pathogenic	-1.949	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/P	0.961	likely_pathogenic	0.966	pathogenic	-1.101	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/Q	0.9702	likely_pathogenic	0.9648	pathogenic	-1.817	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/R	0.9702	likely_pathogenic	0.9621	pathogenic	-1.468	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/S	0.9076	likely_pathogenic	0.9172	pathogenic	-2.516	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/T	0.8456	likely_pathogenic	0.8459	pathogenic	-2.189	Highly Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
V/W	0.9953	likely_pathogenic	0.9955	pathogenic	-1.713	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
V/Y	0.9863	likely_pathogenic	0.9858	pathogenic	-1.34	Destabilizing	1.0	D	0.82	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.