TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8410	25453;25454;25455	chr2:178717646;178717645;178717644	chr2:179582373;179582372;179582371
N2AB	8093	24502;24503;24504	chr2:178717646;178717645;178717644	chr2:179582373;179582372;179582371
N2A	7166	21721;21722;21723	chr2:178717646;178717645;178717644	chr2:179582373;179582372;179582371
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-69
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3457
• 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
F/L	None	None	0.005	D	0.239	0.275	0.296329037015	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85963E-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
F/A	0.8976	likely_pathogenic	0.9267	pathogenic	-2.037	Highly Destabilizing	0.926	D	0.585	neutral	None	None	None	None	N
F/C	0.8399	likely_pathogenic	0.8616	pathogenic	-1.087	Destabilizing	0.999	D	0.655	neutral	D	0.536059777	None	None	N
F/D	0.9709	likely_pathogenic	0.98	pathogenic	-0.448	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
F/E	0.9718	likely_pathogenic	0.9804	pathogenic	-0.367	Destabilizing	0.964	D	0.66	neutral	None	None	None	None	N
F/G	0.9665	likely_pathogenic	0.9787	pathogenic	-2.369	Highly Destabilizing	0.989	D	0.618	neutral	None	None	None	None	N
F/H	0.866	likely_pathogenic	0.8902	pathogenic	-0.673	Destabilizing	0.929	D	0.58	neutral	None	None	None	None	N
F/I	0.5147	ambiguous	0.5913	pathogenic	-1.056	Destabilizing	0.662	D	0.477	neutral	D	0.529248448	None	None	N
F/K	0.9747	likely_pathogenic	0.9818	pathogenic	-1.069	Destabilizing	0.974	D	0.66	neutral	None	None	None	None	N
F/L	0.9446	likely_pathogenic	0.9599	pathogenic	-1.056	Destabilizing	0.005	N	0.239	neutral	D	0.525304066	None	None	N
F/M	0.7731	likely_pathogenic	0.8144	pathogenic	-0.799	Destabilizing	0.629	D	0.567	neutral	None	None	None	None	N
F/N	0.9284	likely_pathogenic	0.9465	pathogenic	-1.09	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
F/P	0.9974	likely_pathogenic	0.9985	pathogenic	-1.374	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
F/Q	0.9566	likely_pathogenic	0.9699	pathogenic	-1.143	Destabilizing	0.988	D	0.665	neutral	None	None	None	None	N
F/R	0.9392	likely_pathogenic	0.955	pathogenic	-0.456	Destabilizing	0.974	D	0.663	neutral	None	None	None	None	N
F/S	0.8334	likely_pathogenic	0.8824	pathogenic	-1.94	Destabilizing	0.985	D	0.609	neutral	N	0.505928871	None	None	N
F/T	0.8502	likely_pathogenic	0.8926	pathogenic	-1.763	Destabilizing	0.978	D	0.607	neutral	None	None	None	None	N
F/V	0.4986	ambiguous	0.5661	pathogenic	-1.374	Destabilizing	0.586	D	0.5	neutral	N	0.505966156	None	None	N
F/W	0.7033	likely_pathogenic	0.7543	pathogenic	-0.269	Destabilizing	0.995	D	0.567	neutral	None	None	None	None	N
F/Y	0.3228	likely_benign	0.3461	ambiguous	-0.467	Destabilizing	0.002	N	0.229	neutral	N	0.471989656	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.