TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34224	102895;102896;102897	chr2:178533945;178533944;178533943	chr2:179398672;179398671;179398670
N2AB	32583	97972;97973;97974	chr2:178533945;178533944;178533943	chr2:179398672;179398671;179398670
N2A	31656	95191;95192;95193	chr2:178533945;178533944;178533943	chr2:179398672;179398671;179398670
N2B	25159	75700;75701;75702	chr2:178533945;178533944;178533943	chr2:179398672;179398671;179398670
Novex-1	25284	76075;76076;76077	chr2:178533945;178533944;178533943	chr2:179398672;179398671;179398670
Novex-2	25351	76276;76277;76278	chr2:178533945;178533944;178533943	chr2:179398672;179398671;179398670
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-160
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0794
• 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
L/I	None	None	0.999	N	0.582	0.39	0.444102476654	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
L/A	0.9298	likely_pathogenic	0.9172	pathogenic	-2.801	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
L/C	0.9363	likely_pathogenic	0.9258	pathogenic	-1.642	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/D	0.9974	likely_pathogenic	0.9974	pathogenic	-3.316	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
L/E	0.9901	likely_pathogenic	0.9891	pathogenic	-2.99	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/F	0.7355	likely_pathogenic	0.7574	pathogenic	-1.712	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/G	0.9835	likely_pathogenic	0.9752	pathogenic	-3.406	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/H	0.971	likely_pathogenic	0.972	pathogenic	-3.103	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/I	0.27	likely_benign	0.2943	benign	-0.97	Destabilizing	0.999	D	0.582	neutral	N	0.48787424	None	None	N
L/K	0.9769	likely_pathogenic	0.9758	pathogenic	-1.963	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/M	0.4038	ambiguous	0.3983	ambiguous	-1.007	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/N	0.9764	likely_pathogenic	0.9753	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
L/P	0.9961	likely_pathogenic	0.9963	pathogenic	-1.574	Destabilizing	1.0	D	0.913	deleterious	N	0.518935098	None	None	N
L/Q	0.964	likely_pathogenic	0.9601	pathogenic	-2.309	Highly Destabilizing	1.0	D	0.923	deleterious	N	0.507578792	None	None	N
L/R	0.9648	likely_pathogenic	0.9592	pathogenic	-2.068	Highly Destabilizing	1.0	D	0.92	deleterious	N	0.518935098	None	None	N
L/S	0.9839	likely_pathogenic	0.9815	pathogenic	-3.211	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/T	0.9415	likely_pathogenic	0.9325	pathogenic	-2.724	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/V	0.3592	ambiguous	0.3619	ambiguous	-1.574	Destabilizing	0.999	D	0.575	neutral	N	0.512691767	None	None	N
L/W	0.9648	likely_pathogenic	0.9665	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/Y	0.9444	likely_pathogenic	0.9503	pathogenic	-1.906	Destabilizing	1.0	D	0.905	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.