TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26506	79741;79742;79743	chr2:178566616;178566615;178566614	chr2:179431343;179431342;179431341
N2AB	24865	74818;74819;74820	chr2:178566616;178566615;178566614	chr2:179431343;179431342;179431341
N2A	23938	72037;72038;72039	chr2:178566616;178566615;178566614	chr2:179431343;179431342;179431341
N2B	17441	52546;52547;52548	chr2:178566616;178566615;178566614	chr2:179431343;179431342;179431341
Novex-1	17566	52921;52922;52923	chr2:178566616;178566615;178566614	chr2:179431343;179431342;179431341
Novex-2	17633	53122;53123;53124	chr2:178566616;178566615;178566614	chr2:179431343;179431342;179431341
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-81
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0815
• 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	rs371783508	-1.442	0.001	N	0.379	0.228	None	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/F	rs371783508	-1.442	0.001	N	0.379	0.228	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	2.07297E-04	0
L/F	rs371783508	-1.442	0.001	N	0.379	0.228	None	gnomAD-4.0.0	2.10873E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.37354E-05	1.09798E-05	8.00794E-05
L/I	None	None	0.033	N	0.621	0.059	0.335164054921	gnomAD-4.0.0	1.36958E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31879E-05	0
L/P	rs1197368510	None	0.912	D	0.895	0.654	0.855987637376	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1197368510	None	0.912	D	0.895	0.654	0.855987637376	gnomAD-4.0.0	3.84946E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18098E-06	0	0
L/V	None	None	0.001	N	0.269	0.069	0.318540980066	gnomAD-4.0.0	6.84792E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99533E-07	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	0.566	likely_pathogenic	0.4915	ambiguous	-2.923	Highly Destabilizing	0.116	N	0.713	prob.delet.	None	None	None	None	N
L/C	0.6847	likely_pathogenic	0.6477	pathogenic	-2.062	Highly Destabilizing	0.944	D	0.809	deleterious	None	None	None	None	N
L/D	0.9964	likely_pathogenic	0.9953	pathogenic	-3.8	Highly Destabilizing	0.932	D	0.892	deleterious	None	None	None	None	N
L/E	0.9797	likely_pathogenic	0.9758	pathogenic	-3.478	Highly Destabilizing	0.818	D	0.871	deleterious	None	None	None	None	N
L/F	0.2397	likely_benign	0.2215	benign	-1.859	Destabilizing	0.001	N	0.379	neutral	N	0.51811436	None	None	N
L/G	0.9343	likely_pathogenic	0.9102	pathogenic	-3.514	Highly Destabilizing	0.818	D	0.847	deleterious	None	None	None	None	N
L/H	0.9385	likely_pathogenic	0.9342	pathogenic	-3.245	Highly Destabilizing	0.975	D	0.898	deleterious	D	0.546133343	None	None	N
L/I	0.0702	likely_benign	0.0686	benign	-1.129	Destabilizing	0.033	N	0.621	neutral	N	0.495121939	None	None	N
L/K	0.973	likely_pathogenic	0.9733	pathogenic	-2.493	Highly Destabilizing	0.818	D	0.832	deleterious	None	None	None	None	N
L/M	0.1471	likely_benign	0.1353	benign	-1.202	Destabilizing	0.69	D	0.647	neutral	None	None	None	None	N
L/N	0.9771	likely_pathogenic	0.972	pathogenic	-3.263	Highly Destabilizing	0.932	D	0.895	deleterious	None	None	None	None	N
L/P	0.9702	likely_pathogenic	0.9669	pathogenic	-1.721	Destabilizing	0.912	D	0.895	deleterious	D	0.545879854	None	None	N
L/Q	0.9337	likely_pathogenic	0.93	pathogenic	-2.901	Highly Destabilizing	0.932	D	0.879	deleterious	None	None	None	None	N
L/R	0.9484	likely_pathogenic	0.9468	pathogenic	-2.491	Highly Destabilizing	0.773	D	0.874	deleterious	D	0.545879854	None	None	N
L/S	0.9058	likely_pathogenic	0.8752	pathogenic	-3.746	Highly Destabilizing	0.69	D	0.826	deleterious	None	None	None	None	N
L/T	0.6501	likely_pathogenic	0.5913	pathogenic	-3.266	Highly Destabilizing	0.388	N	0.729	prob.delet.	None	None	None	None	N
L/V	0.0646	likely_benign	0.061	benign	-1.721	Destabilizing	0.001	N	0.269	neutral	N	0.494599078	None	None	N
L/W	0.7964	likely_pathogenic	0.79	pathogenic	-2.298	Highly Destabilizing	0.981	D	0.878	deleterious	None	None	None	None	N
L/Y	0.8144	likely_pathogenic	0.8051	pathogenic	-2.099	Highly Destabilizing	0.527	D	0.799	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.