TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29813	89662;89663;89664	chr2:178553568;178553567;178553566	chr2:179418295;179418294;179418293
N2AB	28172	84739;84740;84741	chr2:178553568;178553567;178553566	chr2:179418295;179418294;179418293
N2A	27245	81958;81959;81960	chr2:178553568;178553567;178553566	chr2:179418295;179418294;179418293
N2B	20748	62467;62468;62469	chr2:178553568;178553567;178553566	chr2:179418295;179418294;179418293
Novex-1	20873	62842;62843;62844	chr2:178553568;178553567;178553566	chr2:179418295;179418294;179418293
Novex-2	20940	63043;63044;63045	chr2:178553568;178553567;178553566	chr2:179418295;179418294;179418293
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-105
• Domain position: 80
• Structural Position: 111
• Q(SASA): 0.1859
• 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/L	None	None	0.001	N	0.263	0.071	0.339555952218	gnomAD-4.0.0	1.59116E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85807E-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	0.2818	likely_benign	0.2456	benign	-1.666	Destabilizing	0.22	N	0.518	neutral	N	0.51444678	None	None	I
V/C	0.6513	likely_pathogenic	0.6246	pathogenic	-1.525	Destabilizing	0.968	D	0.624	neutral	None	None	None	None	I
V/D	0.6457	likely_pathogenic	0.6322	pathogenic	-1.827	Destabilizing	0.726	D	0.74	deleterious	None	None	None	None	I
V/E	0.3559	ambiguous	0.3543	ambiguous	-1.796	Destabilizing	0.667	D	0.675	neutral	N	0.481566357	None	None	I
V/F	0.1794	likely_benign	0.1752	benign	-1.339	Destabilizing	0.396	N	0.631	neutral	None	None	None	None	I
V/G	0.3824	ambiguous	0.3425	ambiguous	-1.994	Destabilizing	0.667	D	0.721	prob.delet.	N	0.494510512	None	None	I
V/H	0.5908	likely_pathogenic	0.5849	pathogenic	-1.428	Destabilizing	0.968	D	0.751	deleterious	None	None	None	None	I
V/I	0.0691	likely_benign	0.0686	benign	-0.846	Destabilizing	0.001	N	0.189	neutral	N	0.448107145	None	None	I
V/K	0.3189	likely_benign	0.33	benign	-1.233	Destabilizing	0.567	D	0.681	prob.neutral	None	None	None	None	I
V/L	0.1623	likely_benign	0.1449	benign	-0.846	Destabilizing	0.001	N	0.263	neutral	N	0.502285559	None	None	I
V/M	0.1265	likely_benign	0.1108	benign	-0.873	Destabilizing	0.072	N	0.408	neutral	None	None	None	None	I
V/N	0.4235	ambiguous	0.4004	ambiguous	-1.194	Destabilizing	0.89	D	0.749	deleterious	None	None	None	None	I
V/P	0.9769	likely_pathogenic	0.9735	pathogenic	-1.088	Destabilizing	0.89	D	0.688	prob.neutral	None	None	None	None	I
V/Q	0.3146	likely_benign	0.3071	benign	-1.381	Destabilizing	0.726	D	0.701	prob.neutral	None	None	None	None	I
V/R	0.287	likely_benign	0.295	benign	-0.757	Destabilizing	0.726	D	0.745	deleterious	None	None	None	None	I
V/S	0.3156	likely_benign	0.2959	benign	-1.765	Destabilizing	0.726	D	0.639	neutral	None	None	None	None	I
V/T	0.2136	likely_benign	0.2118	benign	-1.622	Destabilizing	0.272	N	0.475	neutral	None	None	None	None	I
V/W	0.759	likely_pathogenic	0.7499	pathogenic	-1.51	Destabilizing	0.968	D	0.743	deleterious	None	None	None	None	I
V/Y	0.5001	ambiguous	0.501	ambiguous	-1.193	Destabilizing	0.726	D	0.626	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.