TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26110	78553;78554;78555	chr2:178567804;178567803;178567802	chr2:179432531;179432530;179432529
N2AB	24469	73630;73631;73632	chr2:178567804;178567803;178567802	chr2:179432531;179432530;179432529
N2A	23542	70849;70850;70851	chr2:178567804;178567803;178567802	chr2:179432531;179432530;179432529
N2B	17045	51358;51359;51360	chr2:178567804;178567803;178567802	chr2:179432531;179432530;179432529
Novex-1	17170	51733;51734;51735	chr2:178567804;178567803;178567802	chr2:179432531;179432530;179432529
Novex-2	17237	51934;51935;51936	chr2:178567804;178567803;178567802	chr2:179432531;179432530;179432529
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-78
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3434
• 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/P	None	None	0.997	N	0.748	0.477	0.519783508757	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	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
T/A	0.0819	likely_benign	0.087	benign	-0.773	Destabilizing	0.977	D	0.423	neutral	N	0.491257702	None	None	N
T/C	0.4253	ambiguous	0.4305	ambiguous	-0.522	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
T/D	0.3012	likely_benign	0.3075	benign	-0.097	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
T/E	0.2069	likely_benign	0.199	benign	-0.072	Destabilizing	0.966	D	0.644	neutral	None	None	None	None	N
T/F	0.3841	ambiguous	0.376	ambiguous	-0.816	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
T/G	0.2122	likely_benign	0.2233	benign	-1.052	Destabilizing	0.995	D	0.707	prob.neutral	None	None	None	None	N
T/H	0.2272	likely_benign	0.2284	benign	-1.292	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/I	0.2624	likely_benign	0.2765	benign	-0.117	Destabilizing	0.997	D	0.749	deleterious	N	0.503360208	None	None	N
T/K	0.1085	likely_benign	0.1101	benign	-0.676	Destabilizing	0.289	N	0.281	neutral	None	None	None	None	N
T/L	0.1234	likely_benign	0.1263	benign	-0.117	Destabilizing	0.983	D	0.591	neutral	None	None	None	None	N
T/M	0.104	likely_benign	0.1046	benign	-0.006	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
T/N	0.107	likely_benign	0.1111	benign	-0.7	Destabilizing	0.993	D	0.588	neutral	D	0.525484919	None	None	N
T/P	0.2695	likely_benign	0.2761	benign	-0.302	Destabilizing	0.997	D	0.748	deleterious	N	0.48560238	None	None	N
T/Q	0.1374	likely_benign	0.1345	benign	-0.761	Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	N
T/R	0.1193	likely_benign	0.1177	benign	-0.523	Destabilizing	0.99	D	0.681	prob.neutral	None	None	None	None	N
T/S	0.0992	likely_benign	0.1039	benign	-0.977	Destabilizing	0.977	D	0.385	neutral	N	0.4528326	None	None	N
T/V	0.1823	likely_benign	0.1955	benign	-0.302	Destabilizing	0.991	D	0.485	neutral	None	None	None	None	N
T/W	0.7072	likely_pathogenic	0.6976	pathogenic	-0.795	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/Y	0.3694	ambiguous	0.3648	ambiguous	-0.538	Destabilizing	0.999	D	0.791	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.