TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27188	81787;81788;81789	chr2:178564570;178564569;178564568	chr2:179429297;179429296;179429295
N2AB	25547	76864;76865;76866	chr2:178564570;178564569;178564568	chr2:179429297;179429296;179429295
N2A	24620	74083;74084;74085	chr2:178564570;178564569;178564568	chr2:179429297;179429296;179429295
N2B	18123	54592;54593;54594	chr2:178564570;178564569;178564568	chr2:179429297;179429296;179429295
Novex-1	18248	54967;54968;54969	chr2:178564570;178564569;178564568	chr2:179429297;179429296;179429295
Novex-2	18315	55168;55169;55170	chr2:178564570;178564569;178564568	chr2:179429297;179429296;179429295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-86
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1377
• 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
T/I	None	None	0.949	N	0.72	0.312	0.399596177874	gnomAD-4.0.0	1.36877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79911E-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
T/A	0.154	likely_benign	0.135	benign	-1.017	Destabilizing	0.349	N	0.557	neutral	N	0.516750792	None	None	N
T/C	0.4614	ambiguous	0.4541	ambiguous	-0.895	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
T/D	0.6321	likely_pathogenic	0.5491	ambiguous	-1.318	Destabilizing	0.633	D	0.655	neutral	None	None	None	None	N
T/E	0.5178	ambiguous	0.4694	ambiguous	-1.205	Destabilizing	0.775	D	0.665	neutral	None	None	None	None	N
T/F	0.3471	ambiguous	0.3062	benign	-0.708	Destabilizing	0.961	D	0.763	deleterious	None	None	None	None	N
T/G	0.4919	ambiguous	0.4369	ambiguous	-1.371	Destabilizing	0.633	D	0.667	neutral	None	None	None	None	N
T/H	0.3045	likely_benign	0.2872	benign	-1.555	Destabilizing	0.989	D	0.757	deleterious	None	None	None	None	N
T/I	0.2027	likely_benign	0.1964	benign	-0.122	Destabilizing	0.949	D	0.72	prob.delet.	N	0.47390368	None	None	N
T/K	0.2927	likely_benign	0.2799	benign	-0.911	Destabilizing	0.565	D	0.662	neutral	N	0.519617739	None	None	N
T/L	0.157	likely_benign	0.1438	benign	-0.122	Destabilizing	0.775	D	0.663	neutral	None	None	None	None	N
T/M	0.1164	likely_benign	0.1082	benign	-0.061	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
T/N	0.225	likely_benign	0.1899	benign	-1.27	Destabilizing	0.011	N	0.289	neutral	None	None	None	None	N
T/P	0.8266	likely_pathogenic	0.7562	pathogenic	-0.388	Destabilizing	0.949	D	0.718	prob.delet.	N	0.519684523	None	None	N
T/Q	0.3066	likely_benign	0.2882	benign	-1.253	Destabilizing	0.923	D	0.724	prob.delet.	None	None	None	None	N
T/R	0.2704	likely_benign	0.2508	benign	-0.851	Destabilizing	0.901	D	0.693	prob.neutral	N	0.481207834	None	None	N
T/S	0.1503	likely_benign	0.1264	benign	-1.465	Destabilizing	0.034	N	0.411	neutral	N	0.477923045	None	None	N
T/V	0.1687	likely_benign	0.1717	benign	-0.388	Destabilizing	0.775	D	0.585	neutral	None	None	None	None	N
T/W	0.6852	likely_pathogenic	0.6683	pathogenic	-0.773	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
T/Y	0.3564	ambiguous	0.3334	benign	-0.47	Destabilizing	0.987	D	0.762	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.