TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18804	56635;56636;56637	chr2:178599383;178599382;178599381	chr2:179464110;179464109;179464108
N2AB	17163	51712;51713;51714	chr2:178599383;178599382;178599381	chr2:179464110;179464109;179464108
N2A	16236	48931;48932;48933	chr2:178599383;178599382;178599381	chr2:179464110;179464109;179464108
N2B	9739	29440;29441;29442	chr2:178599383;178599382;178599381	chr2:179464110;179464109;179464108
Novex-1	9864	29815;29816;29817	chr2:178599383;178599382;178599381	chr2:179464110;179464109;179464108
Novex-2	9931	30016;30017;30018	chr2:178599383;178599382;178599381	chr2:179464110;179464109;179464108
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: Fn3-24
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.083
• 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/P	None	None	0.968	D	0.943	0.667	0.877731859371	gnomAD-4.0.0	1.64312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.54202E-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	0.8273	likely_pathogenic	0.7863	pathogenic	-2.35	Highly Destabilizing	0.648	D	0.738	prob.delet.	None	None	None	None	N
L/C	0.7727	likely_pathogenic	0.7184	pathogenic	-1.382	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9982	pathogenic	-2.936	Highly Destabilizing	0.929	D	0.935	deleterious	None	None	None	None	N
L/E	0.9941	likely_pathogenic	0.9906	pathogenic	-2.599	Highly Destabilizing	0.929	D	0.922	deleterious	None	None	None	None	N
L/F	0.3438	ambiguous	0.3138	benign	-1.405	Destabilizing	0.866	D	0.742	deleterious	None	None	None	None	N
L/G	0.9817	likely_pathogenic	0.9728	pathogenic	-2.955	Highly Destabilizing	0.929	D	0.918	deleterious	None	None	None	None	N
L/H	0.9813	likely_pathogenic	0.9677	pathogenic	-2.933	Highly Destabilizing	0.993	D	0.921	deleterious	None	None	None	None	N
L/I	0.0745	likely_benign	0.0698	benign	-0.512	Destabilizing	0.004	N	0.33	neutral	N	0.507771524	None	None	N
L/K	0.9895	likely_pathogenic	0.9817	pathogenic	-1.596	Destabilizing	0.929	D	0.911	deleterious	None	None	None	None	N
L/M	0.1908	likely_benign	0.1712	benign	-0.791	Destabilizing	0.866	D	0.724	prob.delet.	None	None	None	None	N
L/N	0.9919	likely_pathogenic	0.986	pathogenic	-2.387	Highly Destabilizing	0.976	D	0.944	deleterious	None	None	None	None	N
L/P	0.9906	likely_pathogenic	0.9862	pathogenic	-1.118	Destabilizing	0.968	D	0.943	deleterious	D	0.548488244	None	None	N
L/Q	0.9777	likely_pathogenic	0.9632	pathogenic	-1.921	Destabilizing	0.991	D	0.946	deleterious	D	0.548488244	None	None	N
L/R	0.9799	likely_pathogenic	0.9646	pathogenic	-1.979	Destabilizing	0.908	D	0.935	deleterious	D	0.548488244	None	None	N
L/S	0.9794	likely_pathogenic	0.9679	pathogenic	-2.819	Highly Destabilizing	0.929	D	0.911	deleterious	None	None	None	None	N
L/T	0.9206	likely_pathogenic	0.8934	pathogenic	-2.309	Highly Destabilizing	0.866	D	0.812	deleterious	None	None	None	None	N
L/V	0.1015	likely_benign	0.0935	benign	-1.118	Destabilizing	0.09	N	0.661	neutral	N	0.500957408	None	None	N
L/W	0.9333	likely_pathogenic	0.9062	pathogenic	-1.736	Destabilizing	0.993	D	0.888	deleterious	None	None	None	None	N
L/Y	0.9143	likely_pathogenic	0.8813	pathogenic	-1.566	Destabilizing	0.929	D	0.847	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.