TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22706	68341;68342;68343	chr2:178578914;178578913;178578912	chr2:179443641;179443640;179443639
N2AB	21065	63418;63419;63420	chr2:178578914;178578913;178578912	chr2:179443641;179443640;179443639
N2A	20138	60637;60638;60639	chr2:178578914;178578913;178578912	chr2:179443641;179443640;179443639
N2B	13641	41146;41147;41148	chr2:178578914;178578913;178578912	chr2:179443641;179443640;179443639
Novex-1	13766	41521;41522;41523	chr2:178578914;178578913;178578912	chr2:179443641;179443640;179443639
Novex-2	13833	41722;41723;41724	chr2:178578914;178578913;178578912	chr2:179443641;179443640;179443639
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: Fn3-52
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4411
• 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	rs765762900	0.119	0.004	N	0.315	0.116	0.242825505644	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs765762900	0.119	0.004	N	0.315	0.116	0.242825505644	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs765762900	0.119	0.004	N	0.315	0.116	0.242825505644	gnomAD-4.0.0	2.564E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78962E-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	0.1546	likely_benign	0.0909	benign	-0.498	Destabilizing	0.055	N	0.51	neutral	N	0.510710254	None	None	N
T/C	0.5221	ambiguous	0.3622	ambiguous	-0.424	Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	N
T/D	0.8449	likely_pathogenic	0.6473	pathogenic	0.178	Stabilizing	0.726	D	0.713	prob.delet.	None	None	None	None	N
T/E	0.7914	likely_pathogenic	0.5812	pathogenic	0.163	Stabilizing	0.726	D	0.667	neutral	None	None	None	None	N
T/F	0.4998	ambiguous	0.2888	benign	-0.622	Destabilizing	0.567	D	0.769	deleterious	None	None	None	None	N
T/G	0.28	likely_benign	0.1541	benign	-0.727	Destabilizing	0.567	D	0.679	prob.neutral	None	None	None	None	N
T/H	0.5705	likely_pathogenic	0.3544	ambiguous	-0.911	Destabilizing	0.968	D	0.761	deleterious	None	None	None	None	N
T/I	0.3373	likely_benign	0.1927	benign	0.005	Stabilizing	0.004	N	0.315	neutral	N	0.502418845	None	None	N
T/K	0.6511	likely_pathogenic	0.4303	ambiguous	-0.547	Destabilizing	0.567	D	0.671	neutral	None	None	None	None	N
T/L	0.1478	likely_benign	0.0916	benign	0.005	Stabilizing	0.026	N	0.477	neutral	None	None	None	None	N
T/M	0.1137	likely_benign	0.0787	benign	0.022	Stabilizing	0.026	N	0.43	neutral	None	None	None	None	N
T/N	0.2366	likely_benign	0.1339	benign	-0.441	Destabilizing	0.667	D	0.581	neutral	N	0.505437721	None	None	N
T/P	0.1434	likely_benign	0.0916	benign	-0.13	Destabilizing	0.859	D	0.735	prob.delet.	N	0.473730734	None	None	N
T/Q	0.4701	ambiguous	0.3104	benign	-0.57	Destabilizing	0.567	D	0.737	prob.delet.	None	None	None	None	N
T/R	0.646	likely_pathogenic	0.4086	ambiguous	-0.309	Destabilizing	0.567	D	0.734	prob.delet.	None	None	None	None	N
T/S	0.1701	likely_benign	0.0982	benign	-0.715	Destabilizing	0.22	N	0.493	neutral	N	0.469207562	None	None	N
T/V	0.2396	likely_benign	0.1463	benign	-0.13	Destabilizing	0.072	N	0.445	neutral	None	None	None	None	N
T/W	0.8233	likely_pathogenic	0.6288	pathogenic	-0.602	Destabilizing	0.968	D	0.773	deleterious	None	None	None	None	N
T/Y	0.5683	likely_pathogenic	0.3596	ambiguous	-0.348	Destabilizing	0.726	D	0.776	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.