TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31569	94930;94931;94932	chr2:178546723;178546722;178546721	chr2:179411450;179411449;179411448
N2AB	29928	90007;90008;90009	chr2:178546723;178546722;178546721	chr2:179411450;179411449;179411448
N2A	29001	87226;87227;87228	chr2:178546723;178546722;178546721	chr2:179411450;179411449;179411448
N2B	22504	67735;67736;67737	chr2:178546723;178546722;178546721	chr2:179411450;179411449;179411448
Novex-1	22629	68110;68111;68112	chr2:178546723;178546722;178546721	chr2:179411450;179411449;179411448
Novex-2	22696	68311;68312;68313	chr2:178546723;178546722;178546721	chr2:179411450;179411449;179411448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-118
• Domain position: 64
• Structural Position: 91
• Q(SASA): 0.144
• Predicted PPI site: I

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
F/L	None	None	0.999	N	0.589	0.455	0.36036328697	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-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
F/A	0.9916	likely_pathogenic	0.9854	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
F/C	0.9094	likely_pathogenic	0.8667	pathogenic	-1.162	Destabilizing	1.0	D	0.799	deleterious	N	0.519289665	None	None	I
F/D	0.9986	likely_pathogenic	0.9975	pathogenic	-1.955	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
F/E	0.9987	likely_pathogenic	0.9978	pathogenic	-1.759	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
F/G	0.9956	likely_pathogenic	0.9933	pathogenic	-2.418	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
F/H	0.9394	likely_pathogenic	0.9191	pathogenic	-0.887	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
F/I	0.9651	likely_pathogenic	0.9394	pathogenic	-0.69	Destabilizing	1.0	D	0.721	prob.delet.	N	0.476724382	None	None	I
F/K	0.9982	likely_pathogenic	0.9971	pathogenic	-1.564	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
F/L	0.9944	likely_pathogenic	0.9902	pathogenic	-0.69	Destabilizing	0.999	D	0.589	neutral	N	0.509667317	None	None	I
F/M	0.981	likely_pathogenic	0.9674	pathogenic	-0.442	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
F/N	0.994	likely_pathogenic	0.9901	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
F/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.132	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
F/Q	0.9941	likely_pathogenic	0.9906	pathogenic	-1.923	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
F/R	0.9926	likely_pathogenic	0.9892	pathogenic	-1.229	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
F/S	0.9856	likely_pathogenic	0.976	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.745	deleterious	D	0.533305326	None	None	I
F/T	0.9945	likely_pathogenic	0.9901	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
F/V	0.9495	likely_pathogenic	0.9158	pathogenic	-1.132	Destabilizing	1.0	D	0.654	neutral	N	0.465222584	None	None	I
F/W	0.8912	likely_pathogenic	0.8683	pathogenic	0.155	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
F/Y	0.2558	likely_benign	0.2285	benign	-0.143	Destabilizing	0.999	D	0.5	neutral	N	0.440959381	None	None	I

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.