TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5808	17647;17648;17649	chr2:178731344;178731343;178731342	chr2:179596071;179596070;179596069
N2AB	5491	16696;16697;16698	chr2:178731344;178731343;178731342	chr2:179596071;179596070;179596069
N2A	4564	13915;13916;13917	chr2:178731344;178731343;178731342	chr2:179596071;179596070;179596069
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-41
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.6221
• 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
A/S	None	None	1.0	N	0.63	0.355	0.378498632473	gnomAD-4.0.0	1.59127E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85838E-06	0	0
A/V	rs1409068952	None	1.0	D	0.669	0.371	0.449088463789	gnomAD-4.0.0	1.36843E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79896E-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
A/C	0.7837	likely_pathogenic	0.7757	pathogenic	-0.879	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
A/D	0.9344	likely_pathogenic	0.9316	pathogenic	-0.67	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
A/E	0.9119	likely_pathogenic	0.9061	pathogenic	-0.823	Destabilizing	1.0	D	0.728	prob.delet.	N	0.492546546	None	None	I
A/F	0.6655	likely_pathogenic	0.7155	pathogenic	-0.981	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
A/G	0.3394	likely_benign	0.3531	ambiguous	-0.279	Destabilizing	1.0	D	0.593	neutral	N	0.487493663	None	None	I
A/H	0.9272	likely_pathogenic	0.9345	pathogenic	-0.233	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
A/I	0.6369	likely_pathogenic	0.6422	pathogenic	-0.482	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
A/K	0.977	likely_pathogenic	0.9784	pathogenic	-0.601	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
A/L	0.6296	likely_pathogenic	0.636	pathogenic	-0.482	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
A/M	0.6618	likely_pathogenic	0.6777	pathogenic	-0.603	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
A/N	0.8667	likely_pathogenic	0.8751	pathogenic	-0.316	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
A/P	0.9771	likely_pathogenic	0.9776	pathogenic	-0.392	Destabilizing	1.0	D	0.729	prob.delet.	D	0.527540515	None	None	I
A/Q	0.9093	likely_pathogenic	0.916	pathogenic	-0.597	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
A/R	0.9281	likely_pathogenic	0.9355	pathogenic	-0.13	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
A/S	0.231	likely_benign	0.2314	benign	-0.484	Destabilizing	1.0	D	0.63	neutral	N	0.515551219	None	None	I
A/T	0.3846	ambiguous	0.369	ambiguous	-0.569	Destabilizing	1.0	D	0.703	prob.neutral	D	0.524245151	None	None	I
A/V	0.3387	likely_benign	0.3253	benign	-0.392	Destabilizing	1.0	D	0.669	neutral	D	0.524938706	None	None	I
A/W	0.9625	likely_pathogenic	0.9694	pathogenic	-1.064	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
A/Y	0.8708	likely_pathogenic	0.889	pathogenic	-0.761	Destabilizing	1.0	D	0.774	deleterious	None	None	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.