TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5282	16069;16070;16071	chr2:178733449;178733448;178733447	chr2:179598176;179598175;179598174
N2AB	4965	15118;15119;15120	chr2:178733449;178733448;178733447	chr2:179598176;179598175;179598174
N2A	4038	12337;12338;12339	chr2:178733449;178733448;178733447	chr2:179598176;179598175;179598174
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-36
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0909
• 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
Y/C	rs1253364524	None	0.002	N	0.514	0.26	0.0611884634855	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
Y/C	rs1253364524	None	0.002	N	0.514	0.26	0.0611884634855	gnomAD-4.0.0	6.40494E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19649E-05	0	0
Y/D	rs1438275064	-3.303	0.81	N	0.81	0.423	0.500868654924	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
Y/D	rs1438275064	-3.303	0.81	N	0.81	0.423	0.500868654924	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
Y/D	rs1438275064	-3.303	0.81	N	0.81	0.423	0.500868654924	gnomAD-4.0.0	2.56281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78657E-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
Y/A	0.7925	likely_pathogenic	0.8485	pathogenic	-2.802	Highly Destabilizing	0.25	N	0.712	prob.delet.	None	None	None	None	N
Y/C	0.1564	likely_benign	0.1834	benign	-1.639	Destabilizing	0.002	N	0.514	neutral	N	0.13592792	None	None	N
Y/D	0.9105	likely_pathogenic	0.9386	pathogenic	-3.431	Highly Destabilizing	0.81	D	0.81	deleterious	N	0.414715052	None	None	N
Y/E	0.9711	likely_pathogenic	0.9824	pathogenic	-3.206	Highly Destabilizing	0.617	D	0.795	deleterious	None	None	None	None	N
Y/F	0.1241	likely_benign	0.1417	benign	-1.027	Destabilizing	0.712	D	0.636	neutral	N	0.375428129	None	None	N
Y/G	0.7354	likely_pathogenic	0.759	pathogenic	-3.229	Highly Destabilizing	0.617	D	0.791	deleterious	None	None	None	None	N
Y/H	0.7497	likely_pathogenic	0.8264	pathogenic	-2.033	Highly Destabilizing	0.963	D	0.638	neutral	N	0.414715052	None	None	N
Y/I	0.6062	likely_pathogenic	0.6936	pathogenic	-1.381	Destabilizing	0.617	D	0.751	deleterious	None	None	None	None	N
Y/K	0.9721	likely_pathogenic	0.9806	pathogenic	-2.218	Highly Destabilizing	0.617	D	0.78	deleterious	None	None	None	None	N
Y/L	0.6034	likely_pathogenic	0.6501	pathogenic	-1.381	Destabilizing	0.25	N	0.703	prob.neutral	None	None	None	None	N
Y/M	0.7072	likely_pathogenic	0.7726	pathogenic	-1.14	Destabilizing	0.972	D	0.766	deleterious	None	None	None	None	N
Y/N	0.6599	likely_pathogenic	0.7339	pathogenic	-3.13	Highly Destabilizing	0.81	D	0.795	deleterious	N	0.414715052	None	None	N
Y/P	0.9905	likely_pathogenic	0.9931	pathogenic	-1.871	Destabilizing	0.92	D	0.82	deleterious	None	None	None	None	N
Y/Q	0.9519	likely_pathogenic	0.9715	pathogenic	-2.803	Highly Destabilizing	0.92	D	0.774	deleterious	None	None	None	None	N
Y/R	0.9529	likely_pathogenic	0.9697	pathogenic	-2.167	Highly Destabilizing	0.92	D	0.799	deleterious	None	None	None	None	N
Y/S	0.692	likely_pathogenic	0.7616	pathogenic	-3.42	Highly Destabilizing	0.045	N	0.589	neutral	N	0.340059385	None	None	N
Y/T	0.8118	likely_pathogenic	0.8562	pathogenic	-3.065	Highly Destabilizing	0.447	N	0.764	deleterious	None	None	None	None	N
Y/V	0.4597	ambiguous	0.5337	ambiguous	-1.871	Destabilizing	0.447	N	0.711	prob.delet.	None	None	None	None	N
Y/W	0.7508	likely_pathogenic	0.8092	pathogenic	-0.365	Destabilizing	0.992	D	0.657	neutral	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.