TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3022	9289;9290;9291	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497
N2AB	3022	9289;9290;9291	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497
N2A	3022	9289;9290;9291	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497
N2B	2976	9151;9152;9153	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497
Novex-1	2976	9151;9152;9153	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497
Novex-2	2976	9151;9152;9153	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497
Novex-3	3022	9289;9290;9291	chr2:178768772;178768771;178768770	chr2:179633499;179633498;179633497

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-20
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.1275
• 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
T/I	None	None	0.991	N	0.803	0.684	0.570301176191	gnomAD-4.0.0	1.36817E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79859E-06	0	0
T/P	None	None	0.991	D	0.803	0.636	0.578230335649	gnomAD-4.0.0	3.60396E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.94085E-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
T/A	0.1692	likely_benign	0.1671	benign	-0.813	Destabilizing	0.76	D	0.466	neutral	N	0.511832111	None	None	N
T/C	0.5235	ambiguous	0.5721	pathogenic	-0.646	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
T/D	0.7682	likely_pathogenic	0.7889	pathogenic	-1.156	Destabilizing	0.986	D	0.717	prob.delet.	None	None	None	None	N
T/E	0.6023	likely_pathogenic	0.5774	pathogenic	-1.095	Destabilizing	0.986	D	0.723	prob.delet.	None	None	None	None	N
T/F	0.4036	ambiguous	0.3806	ambiguous	-0.714	Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
T/G	0.5485	ambiguous	0.5697	pathogenic	-1.132	Destabilizing	0.91	D	0.64	neutral	None	None	None	None	N
T/H	0.3314	likely_benign	0.3441	ambiguous	-1.504	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
T/I	0.2332	likely_benign	0.2103	benign	-0.035	Destabilizing	0.991	D	0.803	deleterious	N	0.505669359	None	None	N
T/K	0.3568	ambiguous	0.3213	benign	-0.901	Destabilizing	0.982	D	0.725	prob.delet.	N	0.468278652	None	None	N
T/L	0.1946	likely_benign	0.1524	benign	-0.035	Destabilizing	0.953	D	0.618	neutral	None	None	None	None	N
T/M	0.1248	likely_benign	0.0976	benign	0.228	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
T/N	0.2302	likely_benign	0.2562	benign	-1.122	Destabilizing	0.986	D	0.645	neutral	None	None	None	None	N
T/P	0.8484	likely_pathogenic	0.8225	pathogenic	-0.261	Destabilizing	0.991	D	0.803	deleterious	D	0.584377734	None	None	N
T/Q	0.3071	likely_benign	0.2668	benign	-1.202	Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
T/R	0.293	likely_benign	0.2604	benign	-0.783	Destabilizing	0.982	D	0.808	deleterious	N	0.509482545	None	None	N
T/S	0.1579	likely_benign	0.1849	benign	-1.262	Destabilizing	0.17	N	0.219	neutral	N	0.496511205	None	None	N
T/V	0.1892	likely_benign	0.168	benign	-0.261	Destabilizing	0.953	D	0.524	neutral	None	None	None	None	N
T/W	0.7838	likely_pathogenic	0.7583	pathogenic	-0.769	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
T/Y	0.4566	ambiguous	0.4687	ambiguous	-0.479	Destabilizing	0.998	D	0.792	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.