TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16570	49933;49934;49935	chr2:178613013;178613012;178613011	chr2:179477740;179477739;179477738
N2AB	14929	45010;45011;45012	chr2:178613013;178613012;178613011	chr2:179477740;179477739;179477738
N2A	14002	42229;42230;42231	chr2:178613013;178613012;178613011	chr2:179477740;179477739;179477738
N2B	7505	22738;22739;22740	chr2:178613013;178613012;178613011	chr2:179477740;179477739;179477738
Novex-1	7630	23113;23114;23115	chr2:178613013;178613012;178613011	chr2:179477740;179477739;179477738
Novex-2	7697	23314;23315;23316	chr2:178613013;178613012;178613011	chr2:179477740;179477739;179477738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-8
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1391
• 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/F	rs1345231824	-2.068	1.0	D	0.745	0.478	0.543120768234	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
L/F	rs1345231824	-2.068	1.0	D	0.745	0.478	0.543120768234	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs1345231824	-2.068	1.0	D	0.745	0.478	0.543120768234	gnomAD-4.0.0	6.57981E-06	None	None	None	None	N	None	2.41406E-05	0	None	0	0	None	0	0	0	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
L/A	0.9621	likely_pathogenic	0.9701	pathogenic	-2.783	Highly Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
L/C	0.9345	likely_pathogenic	0.936	pathogenic	-1.919	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9996	pathogenic	-3.516	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/E	0.9946	likely_pathogenic	0.9972	pathogenic	-3.183	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/F	0.7027	likely_pathogenic	0.7016	pathogenic	-1.671	Destabilizing	1.0	D	0.745	deleterious	D	0.713124516	None	None	N
L/G	0.9912	likely_pathogenic	0.9941	pathogenic	-3.405	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/H	0.9915	likely_pathogenic	0.9948	pathogenic	-3.145	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/I	0.1862	likely_benign	0.1949	benign	-0.904	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	N
L/K	0.9913	likely_pathogenic	0.9957	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/M	0.356	ambiguous	0.3671	ambiguous	-1.057	Destabilizing	1.0	D	0.724	prob.delet.	D	0.641370572	None	None	N
L/N	0.9961	likely_pathogenic	0.9977	pathogenic	-2.883	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/P	0.9947	likely_pathogenic	0.9964	pathogenic	-1.522	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/Q	0.9845	likely_pathogenic	0.9914	pathogenic	-2.507	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/R	0.985	likely_pathogenic	0.9919	pathogenic	-2.227	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/S	0.9959	likely_pathogenic	0.9974	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.787153527	None	None	N
L/T	0.977	likely_pathogenic	0.9843	pathogenic	-2.926	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/V	0.2889	likely_benign	0.2928	benign	-1.522	Destabilizing	0.999	D	0.585	neutral	N	0.505676913	None	None	N
L/W	0.9608	likely_pathogenic	0.9751	pathogenic	-2.102	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.787153527	None	None	N
L/Y	0.9739	likely_pathogenic	0.9798	pathogenic	-1.884	Destabilizing	1.0	D	0.821	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.