TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3185	9778;9779;9780	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256
N2AB	3185	9778;9779;9780	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256
N2A	3185	9778;9779;9780	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256
N2B	3139	9640;9641;9642	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256
Novex-1	3139	9640;9641;9642	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256
Novex-2	3139	9640;9641;9642	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256
Novex-3	3185	9778;9779;9780	chr2:178766531;178766530;178766529	chr2:179631258;179631257;179631256

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-22
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.5427
• 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
E/K	None	None	0.992	D	0.575	0.461	0.442567846599	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	2.77439E-05	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
E/A	0.3896	ambiguous	0.3645	ambiguous	-0.781	Destabilizing	0.996	D	0.64	neutral	D	0.568976434	None	None	N
E/C	0.9756	likely_pathogenic	0.9733	pathogenic	-0.52	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/D	0.6903	likely_pathogenic	0.6202	pathogenic	-0.738	Destabilizing	0.996	D	0.494	neutral	D	0.591007689	None	None	N
E/F	0.9753	likely_pathogenic	0.9766	pathogenic	-0.116	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/G	0.7034	likely_pathogenic	0.7063	pathogenic	-1.096	Destabilizing	0.999	D	0.647	neutral	D	0.637129084	None	None	N
E/H	0.9046	likely_pathogenic	0.8963	pathogenic	0.006	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/I	0.7641	likely_pathogenic	0.7792	pathogenic	0.07	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/K	0.4347	ambiguous	0.4361	ambiguous	-0.349	Destabilizing	0.992	D	0.575	neutral	D	0.548472214	None	None	N
E/L	0.7263	likely_pathogenic	0.7221	pathogenic	0.07	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/M	0.7643	likely_pathogenic	0.7867	pathogenic	0.239	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/N	0.8219	likely_pathogenic	0.7969	pathogenic	-0.923	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.7378	likely_pathogenic	0.6827	pathogenic	-0.194	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/Q	0.3343	likely_benign	0.3243	benign	-0.803	Destabilizing	0.957	D	0.283	neutral	N	0.501827228	None	None	N
E/R	0.6548	likely_pathogenic	0.6407	pathogenic	0.099	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.6693	likely_pathogenic	0.6456	pathogenic	-1.157	Destabilizing	0.997	D	0.655	neutral	None	None	None	None	N
E/T	0.7073	likely_pathogenic	0.6952	pathogenic	-0.89	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/V	0.5708	likely_pathogenic	0.5821	pathogenic	-0.194	Destabilizing	0.999	D	0.717	prob.delet.	D	0.541029134	None	None	N
E/W	0.9935	likely_pathogenic	0.9942	pathogenic	0.203	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.9643	likely_pathogenic	0.9646	pathogenic	0.149	Stabilizing	1.0	D	0.723	prob.delet.	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.