TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7115	21568;21569;21570	chr2:178723916;178723915;178723914	chr2:179588643;179588642;179588641
N2AB	6798	20617;20618;20619	chr2:178723916;178723915;178723914	chr2:179588643;179588642;179588641
N2A	5871	17836;17837;17838	chr2:178723916;178723915;178723914	chr2:179588643;179588642;179588641
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-55
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1412
• 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/K	None	None	0.79	N	0.468	0.358	0.418095516054	gnomAD-4.0.0	6.84364E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99658E-07	0	0
T/S	None	None	0.992	N	0.554	0.308	0.225215365344	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8601E-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	0.1024	likely_benign	0.1003	benign	-1.323	Destabilizing	0.992	D	0.589	neutral	N	0.49917246	None	None	N
T/C	0.5208	ambiguous	0.4973	ambiguous	-0.758	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/D	0.5462	ambiguous	0.5141	ambiguous	-1.9	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
T/E	0.3875	ambiguous	0.3632	ambiguous	-1.612	Destabilizing	0.994	D	0.646	neutral	None	None	None	None	N
T/F	0.2452	likely_benign	0.234	benign	-0.812	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/G	0.3811	ambiguous	0.3598	ambiguous	-1.769	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
T/H	0.2812	likely_benign	0.2639	benign	-1.661	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/I	0.1463	likely_benign	0.1426	benign	-0.106	Destabilizing	1.0	D	0.706	prob.neutral	N	0.493069621	None	None	N
T/K	0.2758	likely_benign	0.2517	benign	-0.184	Destabilizing	0.79	D	0.468	neutral	N	0.455949285	None	None	N
T/L	0.1138	likely_benign	0.1122	benign	-0.106	Destabilizing	0.997	D	0.633	neutral	None	None	None	None	N
T/M	0.1004	likely_benign	0.1035	benign	-0.392	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/N	0.2126	likely_benign	0.1961	benign	-1.131	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
T/P	0.7173	likely_pathogenic	0.7057	pathogenic	-0.485	Destabilizing	1.0	D	0.708	prob.delet.	D	0.538294259	None	None	N
T/Q	0.277	likely_benign	0.2719	benign	-0.713	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
T/R	0.1723	likely_benign	0.1612	benign	-0.648	Destabilizing	0.995	D	0.668	neutral	N	0.460784677	None	None	N
T/S	0.1278	likely_benign	0.1201	benign	-1.337	Destabilizing	0.992	D	0.554	neutral	N	0.456999242	None	None	N
T/V	0.1286	likely_benign	0.1289	benign	-0.485	Destabilizing	0.997	D	0.588	neutral	None	None	None	None	N
T/W	0.6083	likely_pathogenic	0.5848	pathogenic	-1.061	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/Y	0.313	likely_benign	0.2931	benign	-0.64	Destabilizing	1.0	D	0.805	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.