TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8287	25084;25085;25086	chr2:178718147;178718146;178718145	chr2:179582874;179582873;179582872
N2AB	7970	24133;24134;24135	chr2:178718147;178718146;178718145	chr2:179582874;179582873;179582872
N2A	7043	21352;21353;21354	chr2:178718147;178718146;178718145	chr2:179582874;179582873;179582872
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-68
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1183
• 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
V/A	rs2077779717	None	0.95	N	0.673	0.485	0.631562779424	gnomAD-4.0.0	1.60527E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-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
V/A	0.7417	likely_pathogenic	0.7617	pathogenic	-2.388	Highly Destabilizing	0.95	D	0.673	neutral	N	0.475502469	None	None	N
V/C	0.9834	likely_pathogenic	0.9844	pathogenic	-1.42	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
V/D	0.9952	likely_pathogenic	0.9971	pathogenic	-3.109	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/E	0.9853	likely_pathogenic	0.9902	pathogenic	-2.802	Highly Destabilizing	0.999	D	0.814	deleterious	D	0.579032497	None	None	N
V/F	0.7425	likely_pathogenic	0.7329	pathogenic	-1.374	Destabilizing	0.988	D	0.806	deleterious	None	None	None	None	N
V/G	0.9046	likely_pathogenic	0.9227	pathogenic	-2.973	Highly Destabilizing	0.998	D	0.837	deleterious	D	0.598766493	None	None	N
V/H	0.997	likely_pathogenic	0.9979	pathogenic	-2.767	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/I	0.1006	likely_benign	0.0972	benign	-0.679	Destabilizing	0.031	N	0.201	neutral	None	None	None	None	N
V/K	0.991	likely_pathogenic	0.9946	pathogenic	-1.78	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/L	0.5613	ambiguous	0.6207	pathogenic	-0.679	Destabilizing	0.009	N	0.305	neutral	D	0.537283939	None	None	N
V/M	0.6154	likely_pathogenic	0.6547	pathogenic	-0.719	Destabilizing	0.989	D	0.733	prob.delet.	D	0.578628889	None	None	N
V/N	0.9893	likely_pathogenic	0.9932	pathogenic	-2.396	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/P	0.9906	likely_pathogenic	0.9942	pathogenic	-1.232	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
V/Q	0.9884	likely_pathogenic	0.9926	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/R	0.9823	likely_pathogenic	0.9891	pathogenic	-1.84	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/S	0.9564	likely_pathogenic	0.965	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/T	0.8005	likely_pathogenic	0.8264	pathogenic	-2.463	Highly Destabilizing	0.997	D	0.698	prob.neutral	None	None	None	None	N
V/W	0.9943	likely_pathogenic	0.9947	pathogenic	-1.918	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/Y	0.9773	likely_pathogenic	0.9781	pathogenic	-1.602	Destabilizing	1.0	D	0.773	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.