TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20873	62842;62843;62844	chr2:178589108;178589107;178589106	chr2:179453835;179453834;179453833
N2AB	19232	57919;57920;57921	chr2:178589108;178589107;178589106	chr2:179453835;179453834;179453833
N2A	18305	55138;55139;55140	chr2:178589108;178589107;178589106	chr2:179453835;179453834;179453833
N2B	11808	35647;35648;35649	chr2:178589108;178589107;178589106	chr2:179453835;179453834;179453833
Novex-1	11933	36022;36023;36024	chr2:178589108;178589107;178589106	chr2:179453835;179453834;179453833
Novex-2	12000	36223;36224;36225	chr2:178589108;178589107;178589106	chr2:179453835;179453834;179453833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-39
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2519
• 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
I/F	None	None	0.001	N	0.375	0.083	0.144782658237	gnomAD-4.0.0	1.59683E-06	None	None	None	None	N	None	0	0	None	0	2.78381E-05	None	0	0	0	0	0
I/T	rs1060500438	None	0.117	N	0.578	0.373	0.531389887418	gnomAD-4.0.0	1.59683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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
I/A	0.4583	ambiguous	0.3225	benign	-2.098	Highly Destabilizing	0.035	N	0.549	neutral	None	None	None	None	N
I/C	0.78	likely_pathogenic	0.739	pathogenic	-1.303	Destabilizing	0.935	D	0.612	neutral	None	None	None	None	N
I/D	0.9788	likely_pathogenic	0.9674	pathogenic	-1.706	Destabilizing	0.791	D	0.702	prob.neutral	None	None	None	None	N
I/E	0.9642	likely_pathogenic	0.9456	pathogenic	-1.569	Destabilizing	0.555	D	0.699	prob.neutral	None	None	None	None	N
I/F	0.2478	likely_benign	0.2328	benign	-1.235	Destabilizing	0.001	N	0.375	neutral	N	0.501221193	None	None	N
I/G	0.9129	likely_pathogenic	0.8554	pathogenic	-2.568	Highly Destabilizing	0.555	D	0.698	prob.neutral	None	None	None	None	N
I/H	0.9449	likely_pathogenic	0.9187	pathogenic	-1.864	Destabilizing	0.935	D	0.685	prob.neutral	None	None	None	None	N
I/K	0.9529	likely_pathogenic	0.9324	pathogenic	-1.541	Destabilizing	0.555	D	0.697	prob.neutral	None	None	None	None	N
I/L	0.1942	likely_benign	0.1686	benign	-0.8	Destabilizing	None	N	0.204	neutral	N	0.466993976	None	None	N
I/M	0.151	likely_benign	0.1243	benign	-0.642	Destabilizing	0.317	N	0.577	neutral	N	0.477764794	None	None	N
I/N	0.8264	likely_pathogenic	0.7557	pathogenic	-1.579	Destabilizing	0.741	D	0.71	prob.delet.	N	0.493667003	None	None	N
I/P	0.7711	likely_pathogenic	0.6813	pathogenic	-1.206	Destabilizing	0.791	D	0.711	prob.delet.	None	None	None	None	N
I/Q	0.9372	likely_pathogenic	0.9045	pathogenic	-1.559	Destabilizing	0.791	D	0.709	prob.delet.	None	None	None	None	N
I/R	0.9219	likely_pathogenic	0.89	pathogenic	-1.148	Destabilizing	0.555	D	0.71	prob.delet.	None	None	None	None	N
I/S	0.7403	likely_pathogenic	0.6116	pathogenic	-2.302	Highly Destabilizing	0.484	N	0.654	neutral	N	0.474802279	None	None	N
I/T	0.3824	ambiguous	0.2468	benign	-2.023	Highly Destabilizing	0.117	N	0.578	neutral	N	0.486412074	None	None	N
I/V	0.083	likely_benign	0.0725	benign	-1.206	Destabilizing	None	N	0.174	neutral	N	0.406057373	None	None	N
I/W	0.9273	likely_pathogenic	0.9207	pathogenic	-1.475	Destabilizing	0.824	D	0.697	prob.neutral	None	None	None	None	N
I/Y	0.7968	likely_pathogenic	0.7808	pathogenic	-1.208	Destabilizing	0.235	N	0.622	neutral	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.